Intravascular devices, systems, and methods to address eye disorders

ABSTRACT

A method may include accessing an artery in communication with an ophthalmic artery of a subject, and advancing a microcatheter along the accessed artery so as to align a distal end of the microcatheter with an ostium of the ophthalmic artery, wherein the microcatheter includes a lumen having a guidewire positioned therein. In addition, the method includes proximally withdrawing the guidewire relative to the microcatheter so as to enable a distal portion of the microcatheter to assume a curved relaxed configuration, and cannulating the ostium with the distal portion of the microcatheter when the distal portion is in the curved relaxed configuration.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims the benefit of priority of U.S. ProvisionalPatent Application No. 62/786,574, filed on Dec. 31, 2018, U.S.Provisional Application No. 62/832,437, filed on Apr. 11, 2019, U.S.Provisional Application No. 62/900,891, filed on Sep. 16, 2019, and U.S.Provisional Application No. 62/908,955, filed on Oct. 1, 2019, each ofwhich is incorporated by reference herein in its entirety.

TECHNICAL FIELD

Aspects of the present disclosure generally relate to intravasculardevices, systems and methods to address eye disorders.

BACKGROUND

Accessing and treating the ophthalmic artery is challenging but couldaddress diseases of the eye. Improvements in devices, systems andmethods for such purposes are needed.

SUMMARY

Blood is supplied to the eye primarily via the internal carotid artery(ICA), ophthalmic artery (OA) and retinal artery (RA). Disease in any ofthese arteries, or elsewhere in the arterial path from the heart, maycompromise blood supply to the eye and contribute to eye disorders suchas age-related macular degeneration (AMD), glaucoma, diabeticretinopathy, among others. Thus, treating such arterial disease mayeffectively treat the associated eye disorder. The inventors have foundthat people with AMD often have arterial disease in the ICA, the ostiumof the OA as it branches off the ICA, and in the short limb of the OA.The devices, systems and methods described herein are intended toprovide improved access and treatment of these vascular targets.

In one embodiment, a method may comprise accessing an oculofacial artery(OFA) at an access site on a face of a patient; advancing a devicethrough OFA access site to an ophthalmic artery (OA); and treating aportion of the OA with the device. In some embodiments, the wherein theOFA comprises the supra-trochlear artery or the supra-orbital artery.

In another embodiment, a method may comprise accessing a superficialtemporal artery (STA) near an ear of a patient; advancing a devicethrough STA access site to an ophthalmic artery (OA); and treating aportion of the OA with the device.

In yet another embodiment, a method may comprise accessing a superficialtemporal artery (STA) near an ear of a patient; advancing a devicethrough STA access site to a cerebral vascular target; and treating aportion of the cerebral vascular target with the device.

In still another embodiment, a method may comprise accessing asuperficial temporal artery (STA) near an ear of a patient; advancing adevice through STA access site to a coronary artery target; and treatinga portion of the coronary artery target with the device.

Further, in one embodiment, a method may comprise accessing an occipitalartery (OcA) near an occipital bone of a patient; advancing a devicethrough OcA access site to an ophthalmic artery (OA); and treating aportion of the OA with the device.

In another embodiment, a method may comprise accessing an occipitalartery (OcA) near an occipital bone of a patient; advancing a devicethrough OcA access site to a cerebral vascular target; and treating aportion of the cerebral vascular target with the device.

In yet another embodiment, a method may comprise accessing an occipitalartery (OcA) near an occipital bone of a patient; advancing a devicethrough OcA access site to a coronary artery target; and treating aportion of the coronary artery target with the device.

In still another embodiment, a device may include a catheter forinsertion through an internal carotid artery (ICA) to reach an ostium ofan ophthalmic artery (OA), wherein the ICA includes clinoid segment justproximal of the OA ostium, wherein the clinoid segment includes aninside bend and an outside bend, the catheter comprising: an elongatetubular shaft having a proximal straight portion, a curved distalportion and a distal tip; the curved portion having a primary curveextending from the straight portion and a secondary curve extending fromthe primary curve; the primary curve having curvature in a firstdirection, the secondary curve having a curvature in a second direction,wherein the first direction is different than the second direction,wherein, when the distal curved portion is positioned in the ICA, theprimary curve engages the outside bend and extends toward the insidebend, and the secondary curve extends from the inside bend toward the OAostium.

In another embodiment, a device may include a catheter for insertionthrough an internal carotid artery (ICA) to reach an ostium of anophthalmic artery (OA), wherein the ICA includes clinoid segment justproximal of the OA ostium, wherein the clinoid segment includes aninside bend and an outside bend, the catheter comprising: an elongatetubular shaft having a proximal straight portion, a curved distalportion and a distal tip; the curved portion having a primary curveextending from the straight portion and a secondary curve extending fromthe primary curve; the primary curve having curvature in a firstdirection, the secondary curve having a curvature in a second direction,wherein the first direction is different than the second direction;wherein the primary curve is configured to engage the outside bend andextend towards the inside bend of the clinoid segment when the distalcurved portion is positioned in the ICA; and wherein the secondary curveis configured to extend from the inside bend of the clinoid segmenttoward the OA ostium when the distal curved portion is positioned in theICA.

In some embodiments, one or more of the following may also apply: thefirst direction is opposite the second direction, the primary curve andthe secondary curve are coplanar, the secondary curve extends from theinside bend to point the distal tip toward the OA ostium, the secondarycurve extends from the inside bend to position the distal tip in the OAostium, the distal tip points at least partially proximally, the primarycurve has a radius of curvature of 7.5 to 15 mm and an arc angle of 35to 55 degrees such that the primary curve has a tighter bend than theinside bend of the clinoid segment, the primary curve has a tighter bendthan the inside bend of the clinoid segment, and/or the secondary curvesubstantially spans the inside bend to the outside bend of the clinoidsegment adjacent the OA ostium.

In yet another embodiment, a method may comprise accessing an artery incommunication with an ophthalmic artery of a subject; advancing amicrocatheter along the accessed artery so as to align a distal end ofthe microcatheter with an ostium of the ophthalmic artery, wherein themicrocatheter includes a lumen having a guidewire positioned therein;proximally withdrawing the guidewire relative to the microcatheter so asto enable a distal portion of the microcatheter to assume a curvedrelaxed configuration; and cannulating the ostium with the distalportion of the microcatheter when the distal portion is in the curvedrelaxed configuration.

In some embodiments, one or more of the following may also apply: aftercannulating the ostium with the distal portion of the microcatheter,advancing the guidewire into the ophthalmic artery; before proximallywithdrawing the guidewire, inflating a balloon within one of a cervicalsegment, a petrous segment, or a lacerum segment of an internal carotidartery; in the curved relaxed configuration, the distal portion of themicrocatheter corresponds to a shape of a shepherd's hook; t performingan angioplasty procedure via a balloon; and/or the accessed artery is aninternal carotid artery, and during the angioplasty procedure, theballoon is located in one of the ophthalmic artery, the ostium, orextending partially within the internal carotid artery and into a shortlimb of the ophthalmic artery.

In still another embodiment, a method may comprise accessing an internalcarotid artery in communication with an ophthalmic artery of a subject;advancing a microcatheter along the internal carotid artery so as toalign a distal end of the microcatheter with an ostium between theinternal carotid artery and the ophthalmic artery, wherein themicrocatheter includes a lumen having a guidewire positioned therein;proximally withdrawing the guidewire relative to the microcatheter so asto enable a distal portion of the microcatheter to assume a curvedrelaxed configuration, wherein, in the curved relaxed configuration, acentral longitudinal axis of the distal portion includes at least afirst curve in a first direction and a second curve in a seconddirection different than the first direction; and cannulating the ostiumvia the distal portion of the microcatheter when the distal portion isin the curved relaxed configuration.

In some embodiments, one or more of the following may also apply:delivering the microcatheter to the internal carotid artery via adelivery artery, wherein the delivery artery is one of a supra-orbitalartery, a supra-trochlear artery, a superficial temporal artery, or anoccipital artery; before proximally withdrawing the guidewire, inflatinga balloon within one of a cervical segment, a petrous segment, or alacerum segment of the internal carotid artery; in the curved relaxedconfiguration, the distal portion of the microcatheter corresponds to ashape of a shepherd's hook; the seating the first curve in one of anophthalmic segment or a communicating segment of the internal carotidartery, and seating the second curve in one of a clinoid segment or anophthalmic segment of the internal carotid artery to stabilize themicrocatheter; a radius of curvature of the first curve is larger than aradius of curvature of the second curve; in the curved relaxedconfiguration, the central longitudinal axis of the distal portion ofthe microcatheter further includes a third curve in a third direction; aradius of curvature of the first curve is larger than a radius ofcurvature of the second curve, and the radius of curvature of the secondcurve is larger than a radius of curvature of the third curve;performing an angioplasty procedure via a balloon; and/or, during theangioplasty procedure, the balloon is located in one of the ophthalmicartery, the ostium between the ophthalmic artery and the internalcarotid artery, or extending partially within the internal carotidartery and into a short limb of the ophthalmic artery.

Further, in one embodiment, a method may comprise accessing an internalcarotid artery in communication with an ophthalmic artery of a subject;advancing a support catheter along the internal carotid artery; stoppingantegrade flow within the internal carotid artery by inflating a balloonof the support catheter within one of a cervical segment, a petroussegment, or a lacerum segment of the internal carotid artery; advancinga microcatheter along the internal carotid artery via the supportcatheter so as to align a distal end of the microcatheter with an ostiumbetween the internal carotid artery and the ophthalmic artery, whereinthe microcatheter includes a lumen having a guidewire positionedtherein; proximally withdrawing the guidewire relative to themicrocatheter so as to enable a distal portion of the microcatheter toassume a curved relaxed configuration, wherein, in the curved relaxedconfiguration, a central longitudinal axis of the distal portionincludes at least a first curve in a first direction and a second curvein a second direction different than the first direction; andcannulating the ostium via the distal portion of the microcatheter whenthe distal portion is in the curved relaxed configuration.

In some embodiments, one or more of the following may also apply: in thecurved relaxed configuration, the distal portion of the microcathetercorresponds to a shape of a shepherd's hook; seating the first curve inone of an ophthalmic segment or a communicating segment of the internalcarotid artery, and seating the second curve in one of a clinoid segmentor an ophthalmic segment of the internal carotid artery to stabilize themicrocatheter; and/or performing an angioplasty procedure in one of theophthalmic artery, the ostium between the internal carotid artery andthe ophthalmic artery, or partially within the internal carotid arteryand a short limb of the ophthalmic artery.

In yet another embodiment, a method may comprise accessing an artery incommunication with an ophthalmic artery of a subject; advancing aballoon microcatheter along the accessed artery so as to align a distalend of the balloon microcatheter with an ostium of the ophthalmicartery, wherein the balloon microcatheter includes a lumen having aguidewire positioned therein; proximally withdrawing the guidewirerelative to the balloon microcatheter so as to enable a distal portionof the balloon microcatheter to assume a curved relaxed configuration;cannulating the ostium with the distal portion of the balloonmicrocatheter when the distal portion is in the curved relaxedconfiguration; and performing a balloon dilation procedure by inflatinga balloon of the balloon microcatheter within the ostium.

In some embodiments, one or more of the following also applies: theaccessed artery is an internal carotid artery, and, during the balloondilation procedure, a distal portion of the balloon is positioned withinthe ostium or the ophthalmic artery, while a proximal portion of theballoon is positioned within the internal carotid artery; during theballoon dilation procedure, no portion of the balloon extends beyond ashort limb of the ophthalmic artery; the balloon microcatheter includesa first wall defining a first lumen and a second wall defining a secondlumen; the proximally withdrawing the guidewire includes proximallywithdrawing the guidewire through the first lumen; an annular spacebetween the first wall and the second wall defines an inflation lumenfor the balloon; in the curved relaxed configuration, a centrallongitudinal axis of the distal portion of the balloon microcatheterincludes at least a first curve in a first direction and a second curvein a second direction different than the first direction; a radius ofcurvature of the first curve is larger than a radius of curvature of thesecond curve; in the curved relaxed configuration, the centrallongitudinal axis of the distal portion further includes a third curve;a radius of curvature of the first curve is larger than a radius ofcurvature of the second curve, and a radius of curvature of the secondcurve is larger than a radius of curvature of the third curve; a shapeof the distal portion of the balloon microcatheter in the curved relaxedconfiguration corresponds to a shepherd's hook; and/or the accessedartery is an internal carotid artery, and, when the distal portion ofthe balloon microcatheter assumes the curved relaxed configuration, themethod further comprises seating the first curve in one of an ophthalmicsegment or a communicating segment of the internal carotid artery, andseating the second curve in one of a clinoid segment or the ophthalmicsegment of the internal carotid artery to stabilize the balloonmicrocatheter.

In another embodiment, a method may comprise accessing an internalcarotid artery in communication with an ophthalmic artery of a subject;advancing a balloon microcatheter along the internal carotid artery soas to align a distal end of the balloon microcatheter with an ostium ofthe ophthalmic artery, wherein the balloon microcatheter includes alumen having a guidewire positioned therein; proximally withdrawing theguidewire relative to the balloon microcatheter so as to enable a distalportion of the balloon microcatheter to assume a curved relaxedconfiguration, wherein, in the curved relaxed configuration, a centrallongitudinal axis of the distal portion includes at least a first curvein a first direction and a second curve in a second direction differentthan the first direction; cannulating the ostium with the distal portionof the balloon microcatheter when the distal portion is in the curvedrelaxed configuration; and performing an angioplasty procedure byinflating a balloon of the balloon microcatheter within the ostium,wherein, during the performing the angioplasty, no portion of theballoon extends beyond a short limb of the ophthalmic artery.

In some embodiments, one or more of the following may also apply: duringthe balloon dilation procedure, a distal portion of the balloon ispositioned within the ostium or the ophthalmic artery, while a proximalportion of the balloon is positioned within the internal carotid artery;the lumen having the guidewire positioned therein is a first lumen, andwherein the balloon microcatheter includes a first wall defining thefirst lumen and a second wall defining a second lumen; the inflating theballoon includes delivering inflation fluid to the balloon via thesecond lumen, wherein the second lumen is arranged between the firstwall and the second wall; a radius of curvature of the first curve isgreater than a radius of curvature of the second curve; a shape of thedistal portion of the balloon microcatheter in the curved relaxedconfiguration corresponds to a shepherd's hook; and/or, when the distalportion of the balloon microcatheter assumes the curved relaxedconfiguration, the method further comprises seating the first curve inone of an ophthalmic segment or a communicating segment of the internalcarotid artery, and seating the second curve in one of a clinoid segmentor the ophthalmic segment of the internal carotid artery to stabilizethe balloon microcatheter.

In yet another aspect, a method may comprise accessing an internalcarotid artery in communication with an ophthalmic artery of a subject;advancing a balloon microcatheter along the internal carotid artery soas to align a distal end of the balloon microcatheter with an ostiumbetween the internal carotid artery and the ophthalmic artery, whereinthe balloon microcatheter includes a lumen having a guidewire positionedtherein; proximally withdrawing the guidewire relative to the balloonmicrocatheter so as to enable a distal portion of the balloonmicrocatheter to assume a curved relaxed configuration, wherein, in thecurved relaxed configuration, a central longitudinal axis of the distalportion includes at least a first curve in a first direction and asecond curve in a second direction different than the first direction;seating the first curve in one of an ophthalmic segment or acommunicating segment of the internal carotid artery, and seating thesecond curve in one of a clinoid segment or an ophthalmic segment of theinternal carotid artery to stabilize the balloon microcatheter;cannulating the ostium via the distal portion of the balloonmicrocatheter when the distal portion is in the curved relaxedconfiguration; and performing an angioplasty procedure by inflating aballoon of the balloon microcatheter within the ostium, wherein, duringthe performing the angioplasty, a distal portion of the balloon ispositioned within the ostium or the ophthalmic artery, a proximalportion of the balloon is positioned within the internal carotid artery,and no portion of the balloon extends beyond a short limb of theophthalmic artery.

In still another embodiment, a microcatheter device may include aproximal portion; and a curved distal portion, the curved distal portionhaving: a first curve segment having a first curve radius in a firstdirection; a second curve segment distal of the first curve segment andhaving a second curve radius extending in a second direction that isdifferent from the first direction; and a third curve segment distal ofthe second curve segment and having a third curve radius, wherein thefirst curve radius is from about 7.5 mm to about 15 mm, the second curveradius is from about 2 mm to about 3 mm, and the third curve radius isabout 1 mm.

In other embodiments, one or more of the following may also apply: thefirst curve, the second curve, and the third curve are co-planar; thefirst direction is opposite to the second direction; the third curveincludes a distal tip, and, when the microcatheter device is insertedinto an internal carotid artery of a subject, the second curve isconfigured to point the distal tip toward an ostium between the internalcarotid artery and an ophthalmic artery of the subject; when themicrocatheter device is inserted into the internal carotid artery of thesubject, the second curve is configured to position the distal tip inthe ostium; the first curve has a tighter bend than a bend of a clinoidsegment of an internal carotid artery of a subject; and/or the firstcurve has an arc angle of 35° to 55°.

In another embodiment, a microcatheter, which is to be introduced intoan internal carotid artery to reach an ostium of an ophthalmic artery,the internal carotid artery including a clinoid segment proximal to theostium, and having an inside bend and an outside bend, may include aproximal straight portion; a curved distal portion having a first curveextending from the straight portion and curving in a first direction,and a second curve extending from the first curve and curving in asecond direction that is different from the first direction; and adistal tip, wherein, when the microcatheter is inserted into theinternal carotid artery, the curved distal portion of the microcatheteris positioned in the internal carotid artery, the first curve engagesthe outside bend of the clinoid segment, and the second curve extendsfrom the inside bend toward the ostium.

In some embodiments, one or more of the following may also apply: thefirst curve and the second curve are co-planar; the first direction isopposite to the second direction; the second curve is configured topoint the distal tip toward the ostium; the second curve is configuredto position the distal tip in the ostium; the first curve has a tighterbend than a bend of the clinoid segment; the first curve has a radius ofcurvature of 7.5 mm to 15 mm and an arc angle of 35° to 55°; the secondcurve has a radius of curvature of 2 mm to 3 mm and an arc angle of 170°to 190°; and/or the curved distal portion further includes a third curveextending from the second curve and having a radius of curvature of 1 mmand an arc angle of 15° to 30°.

In yet another embodiment, a microcatheter device may include a proximalportion; and a curved distal portion, the curved distal portion having:a first curve segment having a first curve radius in a first direction;a second curve segment distal of the first curve segment and having asecond curve radius extending in a second direction that is oppositefrom the first direction; and a third curve segment distal of the secondcurve segment and having a third curve radius, the third curve segmentdefining a distal tip, wherein each of the first curve segment, secondcurve segment, and third curve segment are coplanar, and wherein thecurved distal portion has a shape corresponding to a shepherd's hook.

In some embodiments, one or more of the following may also apply: thefirst curve segment has a radius of curvature of 7.5 mm to 15 mm and anarc angle of 35° to 55°; the second curve segment has a radius ofcurvature of 2 mm to 3 mm and an arc angle of 170° to 190°; and/or thethird curve segment has a radius of curvature of 1 mm and an arc angleof 15° to 30°.

In another embodiment, a method may comprise percutaneously accessing asuperficial temporal artery of a subject; advancing a device in aretrograde direction within the superficial temporal artery of thesubject; advancing the device in the retrograde direction within anexternal carotid artery of the subject; advancing the device within acarotid bifurcation of a common carotid artery of the subject; andadvancing the device in an antegrade direction within an internalcarotid artery of the subject toward an ostium between an ophthalmicartery and the internal carotid artery.

In other embodiments, one or more of the following may also apply:percutaneously accessing the superficial temporal artery includesaccessing the superficial temporal artery through a skin of a subjectproximate to an ear of the subject; advancing the device into theophthalmic artery; the device includes a guidewire and a microcatheter,and the method further comprises proximally withdrawing the guidewirerelative to the microcatheter so as to enable a distal portion of themicrocatheter to assume a curved relaxed configuration; when the distalportion of the microcatheter assumes the curved relaxed configuration, acentral longitudinal axis of the distal portion includes at least firstcurve in a first direction, and a second curve in a second directiondifferent than the first direction; when the distal portion of themicrocatheter assumes the curved relaxed configuration, the first curveis seated in one of an ophthalmic segment or a communicating segment ofthe internal carotid artery, and the second curve is seated in one of aclinoid segment or the ophthalmic segment of the internal carotid arteryto stabilize the microcatheter; a radius of curvature of the first curveis larger than a radius of curvature of the second curve; in the curvedrelaxed configuration, the central longitudinal axis of the distalportion further includes a third curve in a third direction; a radius ofcurvature of the first curve is larger than a radius of curvature of thesecond curve, and the radius of curvature of the second curve is largerthan a radius of curvature of the third curve; cannulating the ostiumvia the distal portion of the microcatheter when the distal portion isin the curved relaxed configuration; the method further comprisesperforming a balloon dilation procedure in the ostium or the ophthalmicartery via a balloon on a distal end of the device; the advancing thedevice in the antegrade direction within the internal carotid arteryincludes advancing the device to one of a cervical segment, a petroussegment, a lacerum segment, or a cavernous segment of the internalcarotid artery; fluidly connecting the device to a reversing system,wherein the reversing system includes a proximal manifold, a commonconduit connected to the proximal manifold, and a reversing manifoldconnected to the common conduit; the reversing manifold comprises aU-turn conduit; and/or the advancing the device includes advancing thedevice via one or more micro motors of the reversing manifold.

In yet another aspect, a method may comprise percutaneously accessing anoccipital artery of a subject; advancing a device in a retrogradedirection within the occipital artery of the subject; advancing thedevice in the retrograde direction within an external carotid artery ofthe subject; advancing the device within a carotid bifurcation of acommon carotid artery of the subject; and advancing the device in anantegrade direction within an internal carotid artery of the subjecttoward an ostium between an ophthalmic artery and the internal carotidartery of the subject.

In addition, one or more of the following may also apply: advancing thedevice into the ophthalmic artery; the device includes a guidewire and amicrocatheter, and the method further comprises proximally withdrawingthe guidewire relative to the microcatheter so as to enable a distalportion of the microcatheter to assume a curved relaxed configuration; ashape of the distal portion of the microcatheter in the curved relaxedconfiguration corresponds to a shepherd's hook; when the distal portionof the microcatheter assumes the curved relaxed configuration, a centrallongitudinal axis of the distal portion includes at least first curve ina first direction, and a second curve in a second direction differentthan the first direction; when the distal portion of the microcatheterassumes the curved relaxed configuration, the first curve is seated inone of an ophthalmic segment or a communicating segment of the internalcarotid artery, and the second curve is seated in one of a clinoidsegment or the ophthalmic segment of the internal carotid artery tostabilize the microcatheter; cannulating the ostium via the distalportion of the microcatheter when the distal portion is in the curvedrelaxed configuration; the advancing the device in the antegradedirection within the internal carotid artery includes advancing thedevice to one of a cervical segment, a petrous segment, a lacerumsegment, or a cavernous segment of the internal carotid artery; and/orpercutaneously accessing the occipital artery includes accessing theoccipital artery through a skin of the subject proximate to an occipitalbone of the subject.

In still another aspect, a method may comprise percutaneously accessinga superficial temporal artery of a subject; advancing a device in aretrograde direction within the superficial temporal artery of thesubject, the device including a guidewire, a microcatheter, and aballoon at a distal end of the microcatheter; advancing the device inthe retrograde direction within an external carotid artery of thesubject; advancing the device within a carotid bifurcation of a commoncarotid artery of the subject; advancing the device in an antegradedirection within an internal carotid artery of the subject toward anostium between an ophthalmic artery and the internal carotid artery;proximally withdrawing the guidewire relative to the microcatheter so asto enable a distal portion of the microcatheter to assume a curvedrelaxed configuration; and performing a balloon dilation procedure bydilating the balloon of the microcatheter in the ostium or theophthalmic artery.

In another embodiment, the method further comprises seating a firstcurve of the distal portion in one of an ophthalmic segment or acommunicating segment of the internal carotid artery, and seating asecond curve the distal portion in one of a clinoid segment or theophthalmic segment of the internal carotid artery to stabilize themicrocatheter.

In another embodiment, a method may comprise acquiring an opticalcoherence tomography (OCT) en face image of a target anatomy of asubject; acquiring one or more OCT cross-sectional images of the targetanatomy; identifying one or more dark areas in the acquired OCT en faceimage; selecting one or more OCT cross-sectional images corresponding tothe identified one or more OCT en face image dark areas; identifying oneor more dark areas in each of the selected OCT cross-sectional images;identifying one or more layers in each of the selected one or more OCTcross-sectional images in which photoreceptors reside; determiningwhether the identified one or more OCT cross-sectional image dark areasreside within the identified one or more layers; and, when thedetermining step determines a majority of the identified one or more OCTcross-sectional image dark areas reside within the one or moreidentified layers, indicating a treatment for arterial disease.

In some embodiments, one or more of the following may also apply: thetarget anatomy is a fovea of the subject; in the step of acquiring theOCT en face image of at least the fovea, an OCT en face image of thefovea, macula, and at least a majority of a retina of the subject isacquired; the OCT cross-sectional images include cross-sectional imagesof eye tissue and layers from a retina to a choroid of the subject; thetreatment for arterial disease includes treating at least one of ablockage, a stenosis, a lesion, plaque, or other physiology of thesubject; and/or the treatment includes balloon dilation.

In yet another embodiment, a method may comprise acquiring an opticalcoherence tomography (OCT) en face image of a fovea of a subject;acquiring one or more OCT cross-sectional images of the fovea, the OCTcross-sectional images including cross-sectional images of eye tissueand layers from a retina to a choroid of the subject; identifying one ormore dark areas in the acquired OCT en face image; selecting one or moreOCT cross-sectional images corresponding to the identified one or moreOCT en face image dark areas; identifying one or more dark areas in eachof the selected OCT cross-sectional images; identifying one or morelayers in each of the selected one or more OCT cross-sectional images inwhich photoreceptors reside; determining whether the identified one ormore OCT cross-sectional image dark areas reside within the identifiedone or more layers; and, when the determining step determines a majorityof the identified one or more OCT cross-sectional image dark areasreside within the one or more identified layers, indicating a treatmentfor arterial disease.

In some embodiments, one or more of the following may also apply: in thestep of acquiring the OCT en face image of at least the fovea, an OCT enface image of the fovea, macula, and at least a majority of the retinaof the subject is acquired; the treatment for arterial disease includestreating at least one of a blockage, a stenosis, a lesion, plaque, orother physiology of the subject; the treatment includes balloondilation; the balloon dilation includes balloon dilation of anophthalmic artery of the subject; and/or the arterial disease includesone or more of age-related macular degeneration (AMD), glaucoma, ordiabetic retinopathy.

In still another embodiment, a method may comprise acquiring an opticalcoherence tomography (OCT) en face image of a fovea of a subject;acquiring one or more OCT cross-sectional images of the fovea;identifying one or more dark areas in the acquired OCT en face image;selecting one or more OCT cross-sectional images corresponding to theidentified one or more OCT en face image dark areas; identifying one ormore dark areas in each of the selected OCT cross-sectional images;identifying one or more layers in each of the selected one or more OCTcross-sectional images in which photoreceptors reside; determiningwhether the identified one or more OCT cross-sectional image dark areasreside within the identified one or more layers; and, when thedetermining step determines a majority of the identified one or more OCTcross-sectional image dark areas reside within the one or moreidentified layers, indicating a treatment for arterial disease, thetreatment for arterial disease including treating at least one of ablockage, a stenosis, a lesion, plaque, or other physiology of thesubject, and, when the determining step determines the majority of theidentified one or more OCT cross-sectional image dark areas do notreside within the one or more identified layers, not indicating atreatment for arterial disease.

In some embodiments, one or more of the following may also apply: in thestep of acquiring the OCT en face image of at least the fovea, an OCT enface image of the fovea, macula, and at least a majority of a retina ofthe subject is acquired; the OCT cross-sectional images includecross-sectional images of eye tissue and layers from a retina to achoroid of the subject; the treatment includes balloon dilation; theballoon dilation includes balloon dilation of an ophthalmic artery ofthe subject; the arterial disease includes one or more of age-relatedmacular degeneration (AMD), glaucoma, or diabetic retinopathy; the OCTcross-sectional image is acquired by swept source OCT; and/or the OCTcross-sectional image is acquired by spectral domain OCT.

In another embodiment, a microcatheter may comprise a shaft havingvariable flexibility along a length thereof, the shaft including: amultilayered proximal section including a proximal section outer layer;a multilayered mid-section including a mid-section outer layer that ismore flexible than the proximal section outer layer; a multilayereddistal section including a distal section outer layer that is moreflexible than the mid-section outer layer, and a braid; and a distal tipincluding a variable pitch coil, the variable pitch coil having a distalclosed-gap pitch, a proximal open-gap pitch, and a middle open-gap pitchgreater than the proximal pitch, a distal end of the variable pitch coilterminating proximally of a distalmost end of the distal tip, whereinthe braid of the distal section terminates at a distal end of the distalsection and abuts a proximal end of the variable pitch coil.

In some embodiments, one or more of the following may also apply: anouter diameter of the distal tip is tapered toward the distal end of thedistal tip; the multilayered distal section includes a dual-layer coilof helical hollow strands, wherein the helical hollow strands have anelliptical cross-sectional shape; the proximal section outer layerincludes a polymer, and wherein the multilayered proximal sectionfurther includes a dual-layer coil comprising a helical hollow strand ofwire, a single-layer braid, and an inner liner; the mid-section outerlayer includes a polymer that is more flexible than the polymer of theproximal section outer layer, and wherein the multilayered mid-sectionfurther includes the dual-layer coil comprising the helical hollowstrands of wire, the single-layer braid, and the inner liner; the distalsection outer layer includes a polymer that is more flexible than thepolymer of the mid-section outer layer, and wherein the multilayereddistal section further includes the dual-layer coil comprising thehelical hollow strands of wire, the single-layer braid, and the innerliner; the distal tip further includes a distal tip outer layer; and/ora wall thickness of the distal tip outer layer is greater than a wallthickness of the distal section outer layer.

In yet another embodiment, a may comprise a shaft having variableflexibility along a length thereof, the shaft including: a multilayeredproximal section; a multilayered mid-section that is more flexible thanthe multilayered proximal section; a multilayered distal section that ismore flexible than the multilayered mid-section, the multilayered distalsection including: a distal section outer layer; a dual-layer coilhaving an inner coil layer and an outer layer coil; a single-layerbraid; and an inner liner; and a distal tip including: a distal tipouter layer; a single-layer coil having a distal closed-gap pitch, aproximal open-gap pitch, and a middle open-gap pitch greater than theproximal pitch, wherein the single-layer coil terminates proximally of adistalmost end of the distal tip; and the inner liner, wherein adistal-most end of the single-layer braid abuts the proximal end of thesingle-layer coil at an abutment, wherein the outer layer coil of thedual-layer coil extends over the abutment between the single-layer braidand the proximal end of the single-layer coil, and the inner layer coilof the dual-layer coil terminates at the abutment between thesingle-layer braid and the proximal end of the single-layer coil, andwherein, in a first configuration, a central longitudinal axis of thedistal tip extends along a straight line, while, in a secondconfiguration, the central longitudinal axis of the distal tip iscurved.

In some embodiments, one or more of the following may also apply: anouter diameter of the distal tip is tapered toward the distal end of thedistal tip; the dual-layer coil is formed of helical hollow strands ofwire, wherein the helical hollow strands of wire have an ellipticalcross-sectional shape; the multilayered proximal section includes anouter layer formed of a polymer, the dual-layer coil comprising thehelical hollow strands of wire, the single-layer braid, and the innerliner; the multilayered mid-section includes an outer layer thatincludes a polymer that is more flexible than the polymer of the outerlayer of the proximal section, and wherein the multilayered mid-sectionfurther includes the dual-layer coil comprising the helical hollowstrands of wire, the single-layer braid, and the inner liner; the distalsection outer layer includes a polymer that is more flexible than thepolymer of the mid-section outer layer; and/or the distal tip outerlayer includes a polymer having a wall thickness that is greater than awall thickness of the polymer of the distal section outer layer.

In still another embodiment, a microcatheter may comprise a shaft havingvariable flexibility along a length thereof, the shaft including: aproximal section including a solid core push wire and an outer layer; aplurality of distal sections including: a first multilayered distalsection having a guidewire port at a proximal end; a second multilayereddistal section extending from the first multilayered distal section, thesecond distal multilayered section being more flexible than the firstmultilayered distal section; a third multilayered distal sectionextending from the second multilayered distal section, the thirdmultilayered distal section being more flexible than the secondmultilayered distal section; and a fourth multilayered distal sectionextending from the third multilayered distal section, the fourthmultilayered distal section being more flexible than the thirdmultilayered distal section; and a distal tip including a variable pitchcoil having a distal closed-gap pitch, a proximal open-gap pitch, and amiddle open-gap pitch greater than the proximal pitch.

In some embodiments, one or more of the following may also apply: theouter layer of the proximal section is formed of a polyolefin heatshrink tubing; a diameter of the push wire of the proximal sectiontapers distally from 0.023″ to 0.010″; the distal tip section includes ashape profile, wherein the shape profile includes any one of a straightline, a line with a 45° bend, a line with a 90° bend, a line with a 180°bend, a shepherd's hook, or an abbreviated shepherd's hook; and/or thedistal tip section is formed into a shape of a shepherd's hook having afirst curve in a first direction, and a second curve in a seconddirection that is different from the first direction, wherein the secondcurve extends from a distal end of the first curve.

In another embodiment, a balloon catheter may comprise a shaft extendingbetween a proximal end and a distal end, the shaft including: an innershaft portion extending from the proximal end, through a balloon, to adistal tip, the inner shaft portion having: an inner liner; a metallicsupport middle layer; and an outer layer; and an outer shaft extendingfrom the proximal end to the balloon.

In some embodiments, one or more of the following may also apply: theouter shaft portion has a first flexibility at the proximal end and asecond flexibility at the distal end, wherein the second flexibility isgreater than the first flexibility; the inner liner comprises a polymer,the metallic support middle layer is a coil, and the outer layercomprises a thermoplastic elastomer; the inner liner includes etchedpolytetrafluoroethylene (PTFE), the coil includes spring temper 304vstainless steel, and the thermoplastic elastomer includes PEBAX® 3533; aportion of the inner shaft portion extends distally beyond a distalwaist of the balloon to form the distal tip; the balloon catheter mayfurther comprise at least one marker band provided radially between theinner shaft portion and the balloon at one or more positions; the atleast one marker band is a radiopaque marker band; and/or the at leastone marker band abuts a distal terminus of the coil of the middle layer.

In yet another embodiment, a balloon catheter may comprise a balloon;and a shaft, including: an outer shaft portion, wherein a proximal neckof the balloon is coupled to a distal end of the outer portion; and amultilayered inner shaft portion extending through the balloon to adistal tip, wherein a distal neck of the balloon is coupled to themultilayered inner shaft portion, the multilayered inner shaft portionhaving: an inner liner; a metallic support middle layer; and an outerlayer; wherein each of the outer shaft portion and the inner shaftportion extend between a proximal end of the shaft and a distal end ofthe shaft.

In some embodiments, one or more of the following may also apply: theinner liner comprises a polymer, the metallic support middle layer is acoil, and the outer layer comprises a thermoplastic elastomer; the innerliner includes etched polytetrafluoroethylene (PTFE), the coil includesspring temper 304v stainless steel, and the thermoplastic elastomerincludes PEBAX® 3533; a portion of the inner shaft portion extendsdistally beyond the distal neck of the balloon to form the distal tip;the balloon catheter may further comprise at least one marker bandprovided radially between the inner shaft portion and the balloon at oneor more positions; the at least one marker band is a radiopaque markerband; and/or the at least one marker band abuts a distal terminus of thecoil of the middle layer.

In still another embodiment, a balloon catheter may comprise a cathetershaft outer portion; a catheter shaft inner portion disposed radiallywithin the outer portion and defining a guidewire lumen extendingtherethrough, an annular space between the outer portion and the innerportion defining an inflation lumen; a distal tip section, wherein, in acurved configuration, the distal tip section includes at least a firstcurve in a first direction and a second curve in a second directiondifferent than the first direction; and a balloon in fluid communicationwith the inflation lumen, wherein a proximal neck of the balloon iscoupled to the outer portion and a distal neck of the balloon is coupledto the inner portion.

In some embodiments, one or more of the following may also apply: theouter portion includes a series of increasing flexible polymer tubesfrom a proximal end of the outer portion to a distal end of the outerportion; the balloon catheter further comprises at least one radiopaquemarker provided on the inner portion adjacent to at least one of aproximal end and a distal end of the balloon; the first curve has aradius of approximately 7.5 mm to 15 mm and an arc length ofapproximately 35° to 55°, wherein the second curve has a radius ofapproximately 2 mm to 3 mm and an arc length of approximately 170° to190°; and/or, in the curved configuration, the distal tip sectionincludes a third curve extending from a distal end of the second curve.

In another embodiment, a balloon catheter may comprise a shaftincluding: a tubular proximal shaft section; a tubular mid-shaft sectionextending distally of the proximal shaft section; a core wire extendingfrom the proximal shaft section and into the mid-shaft section; and amulti-lumen tubular distal shaft section extending from the mid-shaftsection, a junction between the distal shaft section and the mid-shaftsection forming a guidewire port, the distal shaft section including aballoon positioned thereon, wherein the junction between the mid-shaftsection and the distal shaft section is configured to burst at apressure that is lower than a burst pressure of the balloon.

In some embodiments, one or more of the following may also apply: thejunction further includes a thermal bond; the thermal bond forms a seal;the balloon has a nominally rated inflation pressure and the junction isconfigured to burst between 1 ATM and 4 ATM above the nominally ratedinflation pressure; the distal shaft section includes an inner portionand an outer portion; the outer portion includes a first polymer, andthe inner portion includes an inner polymeric liner, a metallic middlelayer, and an outer polymeric layer; the distal shaft section furtherincludes a tack bond provided between the outer portion and the innerportion to thereby limit longitudinal movement between the outer portionand the inner portion; and/or the tack bond is configured to transmitlongitudinal push forces between the outer portion and the innerportion.

In yet another embodiment, a balloon catheter may comprise a shaftincluding: a tubular proximal shaft section; a tubular mid-shaft sectionextending distally of the proximal shaft section; a core wire coupled tothe proximal shaft section and extending from the proximal shaft sectionand into the mid-shaft section; and a multi-lumen tubular distal shaftsection extending from the mid-shaft section, a junction between thedistal shaft section and the mid-shaft section forming a guidewire port,the distal shaft section including: a distal outer portion extendingfrom the guidewire port to a balloon, wherein a proximal neck of theballoon is coupled to a distal end of the distal outer portion; and amultilayered inner portion extending from the guidewire port, throughthe balloon, to a distal tip, wherein a distal neck of the balloon iscoupled to the inner portion, and the multilayered inner portion having:an inner liner; a metallic support middle layer; and an outer layer.

In some embodiments, one or more of the following may also apply: thejunction between the mid-shaft section and the distal shaft section isconfigured to burst at a pressure that is lower than a burst pressure ofthe balloon; the junction forms a fluid seal; the balloon has anominally rated inflation pressure and the junction is configured toburst between 1 ATM and 4 ATM above the nominally rated inflationpressure; the distal outer portion includes a first polymer, the innerliner of the multilayered inner portion includes PTFE, the metallicsupport layer of the inner portion includes a stainless steel coil, andthe outer layer of the inner portion includes a second polymer; thedistal shaft section further includes a tack bond provided between thedistal outer portion and the multilayered inner portion to thereby limitlongitudinal movement between the distal outer portion and themultilayered inner portion; and/or the tack bond is configured totransmit longitudinal push forces between the outer portion and theinner portion.

In still another embodiment, a balloon catheter may comprise a shaftincluding: a proximal shaft section; a mid-shaft section extendingdistally of the proximal shaft section; and a distal shaft sectionextending from the mid-shaft section, a junction between the distalshaft section and the mid-shaft section forming a guidewire port, thejunction including a seal, the distal shaft section including: a distalouter portion extending from the guidewire port to a balloon, wherein aproximal neck of the balloon is coupled to a distal end of the distalouter portion; and a multilayered inner portion extending from theguidewire port, through the balloon, to a distal tip, wherein a distalneck of the balloon is coupled to the inner portion, and themultilayered inner portion having: an inner liner; a metallic supportmiddle layer; and an outer layer, wherein the junction between themid-shaft section and the distal shaft section is configured to burst ata pressure that is lower than a burst pressure of the balloon, andwherein the balloon has a nominally rated inflation pressure and thejunction is configured to burst between 1 ATM and 4 ATM above thenominally rated inflation pressure.

In some embodiments, one or more of the following may also apply: thedistal outer portion includes a first polymer, the inner liner includesPTFE, the metallic support layer includes a stainless steel coil, andthe outer layer includes a second polymer; the distal shaft sectionfurther includes a tack bond provided between the distal outer portionand the multilayered inner portion, the tack bond being thermally formedto thereby limit longitudinal movement between the distal outer portionand the multilayered inner portion; the tack bond is configured totransmit longitudinal push forces between the outer portion and theinner portion; and/or the proximal neck of the balloon is thermallybonded to the distal outer portion of the distal shaft section and thedistal neck of the balloon is thermally bonded to the multilayered innerportion of the distal shaft section.

BRIEF DESCRIPTION OF THE DRAWINGS

FIGS. 1-14 are schematic illustrations of a method of access andtreatment of the OA;

FIGS. 15 and 15A-15F are schematic drawings of a balloon access andsupport catheter for use in the method described with reference to FIGS.1-14;

FIGS. 16, 16A, and 16B are schematic drawings of a neuro access andsupport catheter for use in the method described with reference to FIGS.1-14;

FIG. 16C is a chart showing a stiffness profile of a neuro access andsupport catheter according to an embodiment, and stiffness profiles ofexisting devices.

FIGS. 16D-16I are schematic drawings of an alternative rapid exchangeneuro access and support catheter;

FIGS. 17 and 17A-17E are schematic drawings of an over-the-wire aimingmicrocatheter for use in the method described with reference to FIGS.1-14;

FIGS. 18A-18F are schematic drawings of various curves for use on theaiming microcatheter;

FIGS. 19 and 19A are schematic drawings of a rapid exchange aimingmicrocatheter for use in the method described with reference to FIGS.1-14;

FIGS. 20 and 20A-20C are schematic drawings of a rapid exchange microballoon catheter for use in the method described with reference to FIGS.1-14;

FIGS. 20D-20E are schematic drawings of an alternative over-the-wiremicro balloon catheter;

FIG. 21A is a schematic side sectional view of an alternativemicrocatheter;

FIG. 21B is a more detailed schematic side sectional view of the mainproximal shaft of the microcatheter shown in FIG. 21A;

FIG. 21C is a more detailed schematic side sectional view of the distaltip of the microcatheter shown in FIG. 21A;

FIG. 21D is a more detailed schematic side sectional view of thetransition between the main shaft and distal tip of the microcathetershown in FIG. 21A;

FIG. 22A is a schematic side sectional view of an alternative strainrelief for use with the microcatheter shown in FIG. 21A;

FIG. 22B is a perspective view of a torque handle for use with themicrocatheter shown in FIG. 21A;

FIG. 22C is a side cross-sectional view of the torque handle shown inFIG. 22B;

FIGS. 23A-23H are schematic side views of various tip shapes for usewith the microcatheter shown in FIG. 21A;

FIG. 24A is a schematic side sectional view of an alternative ballooncatheter;

FIG. 24B is a schematic side sectional view of an alternative balloonfor use with the balloon catheter shown in FIG. 24A;

FIG. 24C is a more detailed schematic side sectional view of the balloonassembly of the balloon catheter shown in FIG. 24A;

FIG. 24D is a more detailed schematic side sectional view of theballoon, inner and tip assembly of the balloon catheter shown in FIG.24A;

FIG. 24E is a schematic side sectional view of an alternative inner ofthe balloon catheter shown in FIG. 24A;

FIG. 25A is a schematic side sectional view of a guidewire;

FIG. 25B is a more detailed schematic side sectional view of the distalportion of the guidewire shown in FIG. 25A;

FIG. 26A is a schematic side partially-sectioned view of an aimingintermediate catheter;

FIG. 26B is a more detailed schematic side sectional view of the distalportion of the aiming intermediate catheter shown in FIG. 26A;

FIG. 26C is a detailed view of the cut pattern used for the NiTi tube inthe aiming intermediate catheter shown in FIG. 26A;

FIG. 27A is a schematic side partially-sectioned view of an aimingcatheter sheath;

FIG. 27B is a more detailed schematic side sectional view of theproximal and distal shaft portions of the aiming catheter sheath shownin FIG. 27A;

FIG. 27C is a schematic side sectional view of an alternative distalshaft portion of the aiming catheter sheath shown in FIG. 27A;

FIG. 27D is a detailed view of the cut pattern used for the NiTi tube inthe aiming catheter sheath shown in FIG. 27A;

FIGS. 28A and 28B are schematic illustrations of how the aiming catheterand aiming catheter sheath may be used together;

FIGS. 29A and 29B are schematic illustrations of a handle system for usewith the aiming catheter and aiming catheter sheath shown in FIGS. 26Aand 27A, respectively;

FIG. 30 is a schematic side sectional view of a guide sheath;

FIGS. 31A and 31B schematically illustrate how the guidewire,microcatheter, aiming catheter, aiming catheter sheath and guide sheathmay be used together;

FIGS. 32A-32F schematically illustrate various alternative access sitesand associated access and closure accessories;

FIGS. 33A and 33B schematically illustrate an oculofacial approach;

FIG. 33C schematically illustrates a tool to hold an oculofacial arteryfor cannulation;

FIG. 33D schematically illustrates a trocar needle for accessing anoculofacial artery;

FIG. 34A is a schematic side partially-sectioned view of a fixed-wireballoon catheter for use in the oculofacial approach;

FIG. 34B is a more detailed schematic side sectional view of thefixed-wire balloon catheter shown in FIG. 34A;

FIG. 35A is a schematic side sectional view of a distal portion of aninnerless over-the-wire balloon catheter for use in the oculofacialapproach;

FIG. 35B is a schematic side sectional view of a proximal portion of theinnerless over-the-wire balloon catheter shown in FIG. 35A;

FIG. 35C is a schematic side sectional view of a distal portion of aguidewire for use with the innerless over-the-wire balloon cathetershown in FIG. 35A;

FIG. 35D is a cross-sectional view taken along line B-B in FIG. 35C;

FIG. 35E is a more detailed view of the distal portion of the innerlessover-the-wire balloon catheter shown in FIG. 35A;

FIG. 35F is a cross-sectional view taken along line A-A in FIG. 35E;

FIG. 35G schematically illustrates how the innerless over-the-wireballoon catheter shown in FIG. 35A may be used with the guidewire shownin FIG. 35C;

FIGS. 36A-36B are schematic illustrations of a combined femoral andoculofacial approach to stop antegrade flow in the ophthalmic artery,dilate the ophthalmic artery and aspirate if needed;

FIG. 37 schematically illustrates a superficial temporal artery accessapproach;

FIGS. 38A-38E schematically illustrated devices for use in thesuperficial temporal artery access approach;

FIG. 39 is an OCT B Scan (e.g., cross-sectional) image showing variouslayers of the back of the eye;

FIG. 40 is a series of En Face and B Scan (e.g., cross-sectional) OCTimages; and

FIG. 41 is a flow chart of an automated process to determine if dormantphotoreceptors are present and suitable for treatment.

DETAILED DESCRIPTION

In this disclosure, the term “based on” means “based at least in parton.” The singular forms “a,” “an,” and “the” include plural referentsunless the context dictates otherwise. The term “exemplary” is used inthe sense of “example” rather than “ideal.” The terms “comprises,”“comprising,” “includes,” “including,” or other variations thereof, areintended to cover a non-exclusive inclusion such that a process, method,or product that comprises a list of elements does not necessarilyinclude only those elements, but may include other elements notexpressly listed or inherent to such a process, method, article, orapparatus. Relative terms, such as, “substantially” and “generally,” areused to indicate a possible variation of ±10% of a stated or understoodvalue.

The devices, systems and methods described herein are intended toprovide improved access and treatment of vascular disease in arteriessupplying blood to the eye. Such vascular targets may include the ICAnear the OA, the ostium of the OA as it branches off the ICA, or anypart of the OA including the short limb, angle A or the long limb asdescribed by Hayreh, for example. The improved devices may include aguidewire (GW), a neuro access and support catheter (NASC), a balloonaccess and support catheter (BASC), an aiming microcatheter (AMC), amicro balloon catheter (MBC), a diagnostic catheter (DC), an aimingintermediate catheter, an aiming intermediate catheter sheath and aguide sheath, for example. These devices may be used alone or in variouscombinations.

Example Method

Each of the devices described herein may be configured to workcooperatively to reach the OA from an access site in the femoral artery.The diameters and lengths may be adjusted to accommodate differentaccess sites such as the radial, brachial, cervical or common carotidarteries. Less known or heretofore unknown access sites may also beused, such as access from the supra-orbital, supra-trochlear,superficial temporal or occipital arteries. These alternative accesssites are described in more detail hereinafter. For purposes ofillustration, not necessarily limitation, the following descriptionrefers to the femoral access approach.

With reference to FIG. 1, a femoral approach may involve percutaneousaccess into the femoral artery (FA), advancement through the ascendingaorta (AAo), selective cannulation of the right or left common carotidartery (CCA) depending on which eye (right or left) is to be treated,and advancement through the internal carotid artery (ICA) to theophthalmic artery (OA).

With reference to FIG. 2, after percutaneous access into the FA, theBASC (alternatively the NASC) with the DC and 0.035″ GW pre-loadedtherein may be advanced up the FA, AAo and into the AA, using thedesired shape (e.g., Simmons 1, Simmons 2, or Headhunter 1, depending onanatomical geometry) of the DC to selectively cannulate the CCA ofchoice (right or left).

With reference to FIG. 3, the BASC, DC and GW may be advanced into theICA. The ICA may be characterized by segments, where C1 is the cervicalsegment, C2 is the petrous segment, C3 is the lacerum segment, C4 is thecavernous segment, C5 is the clinoid segment, C6 is the ophthalmicsegment and C7 is the communicating segment. In this example, the BASC,DC and GW are advanced together until they reach at least C1 and up toC4.

With reference to FIG. 4, the DC and 0.035″ GW may be removed from theBASC. The AMC over an 0.014″ GW may be advanced through the BASC untilthe GW is positioned beyond C6 and the distal portion of the AMC ispositioned in C6.

With reference to FIG. 5, the BASC may be advanced over the AMC untilthe distal end of the BASC is positioned in C4 or C5. The insidediameter of the BASC may be closely matched to the outside diameter ofthe AMC to mitigate dislodgement of emboli in the ICA by edge effects ofthe BASC.

With reference to FIG. 6, note that the balloon B1 on the BASC may bepositioned approximately 6-10 cm proximal of the distal end of the BASC.Thus, with the distal end of the BASC positioned in C4 or C5 to supportthe AMC and GW for cannulation of the OA, the balloon B1 may be inflatedmore proximally in the ICA such as in segments C1, C2 or C3. SegmentsC1-C3 tend to have less disease as compared to segments C4-C6, thereforeinflating the balloon B1 in this region reduces the likelihood ofembolic dislodgement while still providing distal support of the AMC insegments C4-C6. The balloon B1, while inflated, may serve to cause flowcessation in the ICA and intraprocedural aspiration through the BASC tofurther mitigate the likelihood of a distal embolic event.

As seen in FIG. 7, while the balloon B1 is inflated in C1-C3, the distalend of the AMC is in C6-C7 and the distal end of the GW extends beyondthe distal end of the AMC as shown in FIG. 7, the system is positionedfor cannulation of the OA. As will be described in more detailhereinafter, the AMC may have a distal curvature that may besubstantially straighter when the GW extends therethrough as seen inFIG. 7.

With reference to FIG. 8, the distal curvature of the AMC assumes itsrelaxed state (e.g., similar to a Sheppard's hook) when the GW isretracted in the AMC proximal of the curvature. The distal curvature ofthe AMC may be configured such that it follows the outside contour ofC5-C6, the inside curvature of C6 and extends across the ICA lumen suchthat the distal end of the AMC naturally rests in the ostium of the OAas shown in FIG. 8. This may be referred to as a “microcatheter firsttechnique”, which is different than conventional cannulation techniquesthat use the GW to cannulate first and then the microcatheter isadvanced over the GW. The superior torque response and curve retentionof the AMC, together with its atraumatic tip, allow the AMC to be usedto safely and reliably cannulate the OA while the GW is retractedproximally in the AMC (proximal of the curved tip of the AMC).

With reference to FIG. 9, after successful cannulation of the OA ostiumwith the AMC, the GW may be advanced in the AMC to extend into the OA,such as into the short limb, angle alpha (“A”), or into the long limbbeyond angle A. Positioning the GW beyond angle A provides additionalpurchase of the GW to subsequently support the MBC as it cannulates theOA.

With reference to FIG. 10, once the GW is deep seated in the OA such asbeyond angle A, the AMC may be removed leaving the GW and BASC in place.

With reference to FIGS. 11 and 12, the MBC may be advanced over the GWinside the BASC until the balloon B2 of the MBC is positioned in the OA,OA ostium or bridges the OA ostium from inside the ICA into the OA shortlimb adjacent angle A. Cadaver studies performed by the inventors havedemonstrated that the natural funnel shape of the OA ostium is absent inpeople with eye disorders such as AMD, thus the OA ostium may be atarget for balloon dilation to restore the natural funnel shape. Theballoon B2 may be positioned in the OA proximal of anterior clinoidprocess, specifically the opening of the optic canal in the anteriorclinoid process to avoid dilating the OA against bony structure adjacentthe optic nerve. The distance of the OA origin from the ICA to theopening of optical canal in anterior clinoid process is typically about5 mm, which roughly corresponds to the OA just beyond angle A. As such,note that the balloon B2 is in the short limb proximal of angle A toavoid dilation of angle A and to avoid dilating the OA in the opticalcanal, and note that the balloon B2 is partially in the OA and partiallyin the ICA to effectively dilate the OA ostium. Once in the desiredposition such as the position shown in FIG. 11, the balloon B2 may beinflated to the desired pressure and duration as shown in FIG. 12 torestore a natural funnel shape to the OA ostium.

With reference to FIGS. 13 and 14, the balloon B2 may be deflated andthe MBC may be removed as shown in FIG. 13. Aspiration through the BASCmay be stopped and the balloon B1 may be deflated for subsequent removalas shown in FIG. 14. Thus, this system of devices may be used to restorea natural funnel shape at the OA ostium as shown by the dotted circle inFIG. 14, thereby improving blood flow to the back of the eye andtreating the underlying eye disorder.

The following describes the construction of the devices used in themethods illustrated in FIGS. 1-14. These are given by way of example,not limitation, and alternative devices may be used for similarpurposes, such as the alternative designs described herein.

Balloon Access and Support Catheter (BASC)

With reference to FIG. 15, the BASC 100 is shown schematically. BASC 100may include a dual port manifold 102 comprising molded copolyester(e.g., Tritan MX 731) having a through port 104 for passage of fluidsand devices through the BASC 100 and an inflation port 106 for inflationand deflation of an occlusion balloon 120. BASC 100 may also include astrain relief 108 comprising a molded thermoplastic elastomer (e.g.,PEBAX 3533) to provide stiffness transition from the manifold 102 to theshaft 110. The occlusion balloon 120 may be disposed on a distal portionof the shaft 110, and a distal extension 114 may extend therefrom.Aspirations holes (not shown) may extend through the wall of the distalextension 114 about 1 mm-10 mm distal of the balloon to provideadditional aspiration. A radiopaque marker band 112 may be disposedunder a distal aspect of the balloon 120. The BASC 100, including theelongate shaft 110, occlusion balloon 120 and distal extension 114, mayhave an overall length of about 115 cm, a minimum inside diameter ofabout 0.058″ and a maximum outside diameter of about 0.084″. The distalextension 114 may have a length of about 8.0 cm such that the occlusionballoon 120 is positioned proximal of the distal extremity of the BASC100.

With reference to FIG. 15A which is a detailed view of circle A shown inFIG. 15, and FIG. 15B which is a cross-sectional view taken along lineB-B in FIG. 15A, the elongate shaft 110 may include and inner 130defining a through lumen 116. The inner 130 may be disposed inside anouter 140 defining an annular inflation lumen 118 therebetween. Theocclusion balloon 120 may comprise a thermoplastic polyurethane (e.g.,Tecothane AR-62A) having a proximal end connected to a distal portion ofthe outer 140 and a distal end connected to a distal portion of theinner 130. The distal and proximal ends of the balloon 120 may bethermally bonded to the inner 130 and outer 140, respectively. Thedistal extension 114 may comprise a continuation of the inner 130,absent the outer 140, beyond the distal end of the balloon 120. Theinflatable portion of the balloon 120 may have a length of about 8 mmand an inflated diameter of about 4-10 mm. The distal end of the outer140 may terminate at a midpoint under the balloon 120, and a tack bond150 may connect the distal end of the outer 140 to the inner 130 leavinga crescent-shaped inflation lumen 118 gap of about 0.005″. The tack bond150 may extend a minimum of ⅓^(rd) of the circumference of the interfacebetween the inner 130 and outer 140.

With reference to FIG. 15C, the inner 130 is shown schematically in moredetail. The inner 130 may comprise a multi-layered tube with graduallyincreasing zones of flexibility in the distal direction. For example,the inner 130 may include a proximal support section 132 having a lengthof about 100 cm and an outside diameter of about 0.067″ comprising aninner PTFE liner (e.g., PTFE with PEBAX top coat; 0.058″ insidediameter; 0.00075″ PTFE wall thickness), a wire braid middle layer(e.g., 16 carriers of 0.0015″ diameter 304v/300 KPSI stainless steelpaired wire at 55 picks per inch) and a polyamide outer layer (e.g.,Grilamid L20 or Vestamid Care 21 ML; with a wall thickness inclusive ofbraid of 0.003″ to 0.005″, preferably 0.004″). Extending from theproximal support section 132, the inner 130 may further include aproximal transition section 134 having a length of about 5.0 cm and anoutside diameter of about 0.067″ comprising the same layers as proximalsupport section 132 except the outer layer may comprise a thermoplasticelastomer (e.g., PEBAX 7233; with a wall thickness inclusive of braid of0.003″ to 0.005″, preferably 0.004″). Extending from the proximaltransition section 134, the inner 130 may further include a distaltransition section 136 having a length of about 5.0 cm and an outsidediameter of about 0.067″ comprising the same layers as proximaltransition section 134 except the outer layer may comprise a softerthermoplastic elastomer (e.g., PEBAX 5533; with a wall thicknessinclusive of braid of 0.003″ to 0.005″, preferably 0.004″). Extendingfrom the distal transition section 136, the inner 130 may furtherinclude a distal section 138 having a length of about 9.0 cm and anoutside diameter of about 0.067″ comprising the same inner liner layer,a mid-layer of pattern-cut super-elastic metal tube (e.g., laser cutNiTi tube, polished; 0.00175″ to 0.0025″ wall thickness) and an outerlayer of thermoplastic polyurethane (e.g., Techothane AR-62A; with awall thickness inclusive of NiTi tube of 0.003″).

With reference to FIG. 15E which is a partial cross-sectional view takenalong line E-E in FIG. 15C, the junction between the distal transitionsection 136 and the distal section 138 is shown in more detail. Theinner PTFE liner 131 extends across this junction, with the braid 133abutting the pattern-cut super-elastic metal tube 135, and thethermoplastic elastomer outer layer 137 abutting the thermoplasticpolyurethane 139. A short bridging layer of PET (not shown) may extendacross the braid 133 and the pattern-cut super-elastic metal tube 135under the outer layers 137 and 139. The radiopaque marker band 112(e.g., 90/10 PtIr; approximately 0.9 mm length) may be disposed over thebraid 133 and the pattern-cut super-elastic metal tube 135 andencapsulated by the outer thermoplastic polyurethane layer 139.

With reference to FIG. 15D which is a partial cross-sectional view takenalong line D-D in FIG. 15C, the distal tip of distal extension 138 isshown in more detail. The inner PTFE liner 131 extends through to thedistal end along with the outer thermoplastic polyurethane layer 139.The pattern-cut super-elastic metal tube 135 terminates proximal of thedistal end and is abutted by another radiopaque marker band 113 (e.g.,90/10 PtIr; approximately 0.5 mm length and 0.001″ to 0.0015″ wallthickness) positioned approximately 0.5 mm mm proximal of the distal endand encapsulated by the outer thermoplastic polyurethane layer 139 toform an atraumatic tip.

With reference to FIG. 15F, the outer 140 is shown in more detail. Likethe inner 130, the outer 140 may comprise a multi-layered tube withgradually increasing zones of flexibility in the distal direction. Forexample, the outer 140 may include a proximal section 142 having alength of about 100 cm and an outside diameter of about 0.073″comprising an inner PTFE liner (e.g., PTFE with PEBAX top coat; 0.072″inside diameter; 0.00075 wall thickness), a wire braid middle layer(e.g., 16 carriers of 0.0015″ diameter round wire (or 0.001″×0.003″ flatwire) made of 304v/300 KPSI stainless steel, paired and braided at 50picks per inch) and a thermoplastic polyamide outer layer (e.g.,Grilamid L20; with a wall thickness inclusive of braid of 0.003″ to0.005″, preferably 0.004″). Extending from the proximal section 142, theouter 140 may further include a transition section 144 having a lengthof about 5.0 cm and an outside diameter of about 0.083″ comprising thesame layers as proximal section 142 except the outer layer may comprisea thermoplastic elastomer (e.g., PEBAX 7233; with a wall thicknessinclusive of braid of 0.003″ to 0.005″, preferably 0.004″). Extendingfrom the transition section 144, the outer may further include a distalsection 146 having a length of about 5.0 cm and an outside diameter ofabout 0.083″ comprising the same layers as transition section 144 exceptthe outer layer may comprise a softer thermoplastic elastomer (e.g.,PEBAX 5533; with a wall thickness inclusive of braid of 0.003″ to0.005″, preferably 0.004″). The braid layer may terminate at the end ofthe end of the distal section 146 to define a distal extension 148extending about 5.0 mm to 7.0 mm therefrom that includes the same layersas distal section 146 but excludes the braid and PTFE layers. A shorttube 147 (e.g., PET; 2 mm to 5 mm length, 0.0004″ wall thickness) may beplaced over the distal end of the braid layer at the junction betweenthe distal section 146 and distal extension 148 to prevent the braidfrom protruding post reflow. The various layers may be thermallyre-flowed together using FEP heat shrink and cyanoacrylate adhesivewhere necessary to tack the various components.

When the BASC 100 is fully advanced as shown in FIG. 5, the proximalsection 142 may extend through the FA, AAo and AA to the CC, and thetransition section 144 may extend from the CC to C1 of the ICA. Theballoon 120 may be positioned in C1-C3 of the ICA, and the distalextension 114 may extend through C1 to C5 of the ICA (depending on theposition of the balloon 120), with the distal end residing in C3 to C5of the ICA.

Neuro Access and Support Catheter (NASC)

With reference to FIG. 16, the NASC 200 is shown schematically. NASC 200may include a single port hub 202 comprising molded PET (e.g. Tritan MX731) and a polyolefin heat shrink strain relief 204 connected to theproximal end of a tubular shaft. The tubular shaft may comprisemultilayered materials with gradually increasing flexibility in thedistal direction over an overall length of about 125 cm with an insidediameter of about 0.059 in. The shaft may include a first proximalsupport section 206 about 94 cm long with an outside diameter of about0.081″ which may comprise layers of thermoplastic elastomer (e.g., PEBAX63D; 0.002-0.004″ wall thickness) over polyamide (e.g., Grilamid L20;0.005-0.007″ wall thickness) over stainless steel braid (e.g., 16carrier×0.002″ diameter paired wires at 50 picks per inch diamondpattern) over an inner liner of PTFE (e.g., 0.00075″ wall thickness,0.059″ inside diameter). From the first proximal support section 206, asecond proximal support section 208 extends about 6.0 cm long with anoutside diameter of about 0.075″ and may comprise the same layers asfirst proximal support section 206 excluding the outermost thermoplasticlayer. From the second proximal support section 208, a third proximalsupport section 210 extends about 5.0 cm long with an outside diameterof about 0.073″ and may comprise the same layers as second proximalsupport section 208 except the outermost polyamide layer is replaced bya thermoplastic elastomer layer (e.g., e.g., PEBAX 72D; 0.004-0.006″wall thickness). From the third proximal support section 210, a proximaltransition section 212 extends about 3.0 cm long with an outsidediameter of about 0.073″ and may comprise the same layers as thirdproximal support section 210 except the outermost thermoplasticelastomer layer may comprise a softer thermoplastic elastomer (e.g.,e.g., PEBAX 55D; 0.003-0.005″ wall thickness). From the proximaltransition section 212, a distal transition section 215 extends about4.0 cm long with an outside diameter of about 0.072″ and may comprise anouter layer of thermoplastic polyurethane (e.g., Pellethane 80E;0.003-0.005″ wall thickness) and an inner liner of PTFE (e.g., 0.00075″wall thickness, 0.059″ inside diameter). Between the outer and innerlayers of distal transition section 215, the braid of proximaltransition section 212 continues for about 3 cm and transitions to about1 cm of the coil of distal section 214, with about 1 mm of overlap. Inthe distal transition section 215, a PET heat shrink 216 may be placedunder the thermoplastic polyurethane layer and over the junction wherethe braid covers the coil to bridge the sections together. The distalsection 214 extends about 13.5 cm long with an outside diameter of about0.068″ and may comprise an outer layer of thermoplastic polyurethane(e.g., Tecothane AR-62A; 0.002-0.004″ wall thickness) over a coiled,super-elastic nickel titanium wire (e.g., 0.0015-0.0020″ diameterNitinol wire coiled at 0.006″ pitch) over an inner liner of PTFE (e.g.,0.00075″ wall thickness, 0.059″ inside diameter). From the second distalsection 214, a distal tip 218 extends about 1.5 mm long with an outsidediameter of about 0.069″ which may comprise the same thermoplasticpolyurethane outer layer used in the second distal section 114 over aradiopaque marker band (e.g., 90/10 Pt—Ir; 0.5 mm long) abutting thedistal end of the pattern-cut super-elastic tube over the same PTFEinner liner. The various layers may be thermally re-flowed togetherusing FEP heat shrink and cyanoacrylate adhesive where necessary to tackthe various components.

FIG. 16A, which is a longitudinal cross-section of the NASC 200 takenalong line A-A in FIG. 16, and FIG. 16B, which is a detailed view of thedistal section 214 and distal tip 218 taken along circle B in FIG. 16A,show the layers of the NASC 200 in greater detail, particularly thedistal layers. Specifically, as best seen in FIG. 16B, the distalsection 214 includes an inner PTFE liner 222 and an outer thermoplasticpolyurethane 228. A radiopaque marker band 224 is encapsulated betweeninner and outer layers, with the inner layer 222 terminating under themarker band 224 and the outer layer 228 continuing to form the distaltip section 218. The proximal end of the marker band abuts or covers thedistal end of a super-elastic coil 226 that is also encapsulated betweenthe inner and outer layers. Optionally, a longitudinal member (notshown) such as a polyester suture may be positioned between the innerlayer 222 and coil 226 and extend to the marker band 224 to increase thetensile strength of the distal section 214.

As mentioned previously, the NASC 200 may be used instead of the BASC100 as described with reference to FIGS. 1-14. When the NASC 200 isfully advanced as shown in FIG. 5, first proximal support section 206may extend through the FA, AAo and AA to the CC, and the second proximalsupport section 208 may extend from the CC to C1 of the ICA. The thirdproximal support section 210 and the proximal transition section 212 mayextend through C2 and C3 of the ICA, and the distal section 214 mayextend through C4 and C5 of the ICA, with the distal tip 218 residing inC5 of the ICA.

The stiffness of each of sections 206, 208, 210, 212 and 214 may beconfigured to provide the desired performance as a function of theanatomical locations described above. Based on a 3-point bend testaccording to ASTM Standard F2606, the first proximal support section 206may have a stiffness of about 4.0-9.0 N/mm, or preferably 7.0-8.0 N/mm,which provides a balance of efficient power transfer to sections 208,210, 212 and 214 while avoiding prolapse in the AA. The second proximalsupport section 208 may have a stiffness of about 1.5-4.0 or preferably2.0-3.0 N/mm in order to provide a balance of flexibility in the ICA andsupporting devices extending therethrough while avoiding back-out ofdistal sections 212 and 214. The third proximal support section 210 andthe proximal transition section 212 may have a stiffness of about1.0-3.0 N/mm or preferably 1.5-2.5 N/mm in order to provide a balance offlexibility and support, as well as a more gradual stiffness transitionto the distal section 214. The distal section 214 may have a stiffnessof about 0.15-0.50 or preferably 0.2-0.4 N/mm in order to maintainsupport and power transfer up to C5. An example of the stiffness profileof the NASC 200 compared to two prior art devices (Navien made by ev3;Neuron made by Pnenumbra) is shown in FIG. 16C.

Rapid Exchange (RX) Neuro Access and Support Catheter (NASC)

With reference to FIG. 16D, a RX NASC 250 is shown schematically. RXNASC 250 is similar the NASC 200 but in a rapid exchange configuration.In general, the RX NASC 250 substitutes the proximal shaft sections ofthe NASC 200 with a wire 254 (e.g., 304v ultra spring temper stainlesssteel) and tab 252, while the distal shaft sections of the RX NASC 250may be the same or similar, in terms of construction and materials, tothe proximal transition section 212, distal transition section 215,distal section 214 and distal tip 218 of the NASC 200. The distal end ofthe wire 254 may be connected to a junction 256 which, in turn, may beconnected to the proximal end of the proximal transition section 212.The junction 256 may comprise a single layer of thermoplastic elastomer(e.g., PEBAX 72D; 3.39″ long, 0.004″-0.005″ wall thickness; no PTFEliner). The wire 254 may be bonded to the junction 256 by thermallyreflowing the polymer layer over the wire 254.

With reference to FIGS. 16E and 16F, where FIG. 16E is a schematic sideview and FIG. 16F is a schematic top view, a port in junction 256 may beformed by two skive cuts defining proximal step 262 and distal step 264.The wire 254 may extend through the proximal step 262 and distal step264, stopping short of the proximal transition section 212 to avoidcompromising the luminal opening into the proximal transition section212. By way of example, the skive cuts may be made at an angle of 15degrees and may be spaced about 1.0″ apart, with a distal cut depth ofabout 60% of the overall diameter, and a proximal cut depth of about 80%of the overall diameter, where the overall diameter depends on the sizeof the catheter desired.

By way of example, not limitation: a 4 French RX NASC 250 may have aninside diameter of 0.045″ and an outside diameter of 0.055″; a 5 FrenchRX NASC 250 may have an inside diameter of 0.059″ and an outsidediameter of 0.069″; a 6 French RX NASC 250 may have an inside diameterof 0.073″ and an outside diameter of 0.083″; and a 7 French RX NASC 250may have an inside diameter of 0.086″ and an outside diameter of 0.095″.

With reference to FIGS. 16G-16I, cross-sectional views of the wire 254are shown schematically. By way of example, the cross-section of thewire 254 may have a rounded rectangular shape (FIG. 16G), a rounded Dshape (FIG. 16H) or a rounded crescent shape (FIG. 16I). The wire mayhave a cross-sectional dimension of 0.008″ by 0.020″ for smallerdiameter catheters or 0.012″ by 0.035″ for larger diameter catheters,for example.

The RX NASC 250 provides a number of advantages over conventionalintermediate catheters. The following advantages are given by way ofexample, not limitation.

First, using a proximal wire 254 eliminates a proximal tubular shaft andthus provides improved infusion and aspiration. In other words, theabsence of a proximal tubular shaft leaves the entire (larger) lumen ofguide sheath available for infusion/aspiration. Further, a close distalfit between the RX NASC and the guide sheath ensures that a majority ofthe aspiration happens at the distal tip of the RX NASC 250.

Second, a shorter overlap length between the tubular sections of RX NASC250 with guide sheath allows the RX NASC 250 to be up-sized withoutup-sizing the guide sheath. In other words, the RX NASC 250 can belarger and therefore tighter fitting to guide sheath without introducingdrag/friction and without compromising flushing. For example, aconventional 5 F intermediate catheter is often used with a 6 F guidesheath to provide a relatively large annular gap (e.g., 0.008″ gap) toallow flushing and minimize drag between the devices. While a 6 Fconventional intermediate catheter can be used with a 6 F guide sheath,the resulting annular gap is relatively small (e.g., 0.002″ gap) thatintroduces drag and compromises flushing. A 6 F RX NASC 250 can be usedwith a 6 F guide sheath without introducing excessive drag orcompromising flushing; less drag translates to better catheter movementand an upsized intermediate catheter provides a larger working ID forprocedures requiring larger devices.

Third, the RX NASC 250 has a rapid exchange configuration by virtue ofits side port at junction 256, and thus may be introduced over aconventional length guidewire as opposed to an exchange lengthguidewire.

Fourth, the wire 254 of the RX NASC 250 eliminates a separate flushport. Because the RX NASC 250 uses a wire 254 in place of a proximaltubular section that would otherwise require a separate hub andhemostasis adapter for flushing, the RX NASC 250 may be flushed via theguide sheath flush port. Essentially, two catheters can be flushedsimultaneously through a single y-adapter, and the RX NASC 250 iscompatible with 3 port hemostasis adapters.

Fifth, the wire 254 of the RX NASC may be made in one size to fit avariety of conditions. Conventional intermediate catheters come isvarious lengths (e.g. 115, 120, 125, 130 cm lengths) to be compatiblewith different guide sheaths and different procedures. Having one sizewire 254 sufficiently long to be compatible with all guide sheaths andother devices eliminates the need to stock multiple lengths ofintermediate catheters and thereby reduces hospital inventory.

Sixth, the unique configuration of the RX NASC 250 may be used in otherapplications, such as coronary and peripheral procedures.

Over-the-Wire (OTW) Aiming Microcatheter (AMC)

With reference to FIG. 17, the OTW AMC 300 is shown schematically. OTWAMC 300 may include a single port hub 302 comprising molded PET (e.g.Tritan MX 731) and a molded thermoplastic elastomer (e.g., PEBAX 3533)strain relief 304 connected to the proximal end of a tubular shaft. Thetubular shaft may comprise multilayered materials with graduallyincreasing flexibility in the distal direction over an overall length ofabout 150 cm with an inside diameter of about 0.0165 in. to accommodate0.010″ and 0.014″ guidewires.

The shaft may include a proximal section 306 about 80 cm long with anoutside diameter of about 0.034″ which may comprise layers ofthermoplastic elastomer (e.g., PEBAX 7233; approximately 0.003″ wallthickness) over a dual layer coil over a single layer braid (e.g.,spring temper 304v stainless steel; 16 carrier of 0.0005″×0.0025″ ribbonat 175 picks per inch, diamond pattern) over an inner liner (e.g., PTFE,0.00075″ wall thickness; 0.019″ inside diameter stretched down over amandrel having a diameter of 0.0165″). The dual layer coil may comprisehelical hollow strand 304v stainless steel wire, with the first layercomprising 18 carriers of 0.0012″ diameter wires wound in a right-handdirection and the second layer comprising 18 carriers of 0.0014″diameter wires wound in a left-hand direction, wherein the wound wirelayers have 0.0075″-0.0080″ spaced gaps. The first and second layers maybe swaged down to an overall thickness of about 0.0012″, wherein theswaging process causes the round wires to become elliptical incross-section.

From the proximal section 306, a mid-section 308 extends about 40.0 cmlong with an outside diameter of about 0.034″ and may comprise the samelayers as proximal section 306 except the outer layer may comprise asofter thermoplastic elastomer (e.g., PEBAX 5533; approximately 0.003″wall thickness). From the mid-section 308, a distal section 310 extendsabout 30.0 cm long with an outside diameter of about 0.034″ and maycomprise the same layers as mid-section 308 except the outer layer maycomprise an even softer thermoplastic elastomer (e.g., PEBAX 3533;approximately 0.003″ wall thickness).

From the distal section 310, a distal tip section 312 extends about 1.5cm with an outside diameter that tapers from 0.034″ to 0.0295″ and witha minimum inside diameter of 0.016″. The distal tip section 312 maycomprise an outer layer of thermoplastic elastomer (e.g., PEBAX 3533;approximately 0.002″ wall thickness) over a single layer coil 316 overthe same inner liner (e.g., PTFE, 0.00075″ wall thickness, 0.019″ insidediameter). As seen in FIG. 17D, the coil 316 may comprise 92% Platinum8% Tungsten wire of 0.0025″ diameter wound with a variable pitch. Thepitch may vary from 0.0035″ for the proximal 0.275″, 0.0070″ for themiddle 0.275″ and 0.0025″ (closed gap) for the distal 0.020″ to act as aradiopaque marker band. Alternatively, the coil may comprise 304v springtemper stainless steel 0.001″×0.005″ ribbon wound with a constant pitchof 0.0085″ with a radiopaque marker band swaged on its distal end. Thedistal tip section 312 may include a 1 mm long distal bumper tip 314comprising a continuation of the inner and outer layers without the coil(i.e., the coil and/or marker band terminate 1 mm shy of the distalend).

With reference to FIG. 17A which is a detailed view taken along circle Ain FIG. 17, FIG. 17B which is a detailed view taken along box B in FIG.17A, and FIG. 17C which is a cross-sectional view taken along line C-Cin FIG. 17B, further detail of the junction between distal section 310and the distal tip section 312 is shown. With specific reference to FIG.17C, the inner liner 301 of the distal section continues through boththe distal section 310 and the distal tip section 312. The braid 303terminates at the distal end of the distal section 310 and abuts theproximal end of the coil 309 of the distal tip section 312. Where thedistal end of the braid 303 abuts the proximal end of the coil 309, oneof the layers (e.g., inner layer) of the dual layer coil 305 mayterminate and the other layer (e.g., outer layer) may extend across theabutment to provide a smooth transition, as shown in FIG. 17E. The outerlayer 307 encapsulates the coil layers 305 and 309 of both sections 310and 312.

With reference to FIGS. 18A-18H, which are schematic illustrations ofthe distal tip section 312 of the OTW AMC 300, the distal tip section312 may be formed into a variety of different shapes. For example, thedistal tip section 312 may be straight 330 as shown in FIG. 18A, or mayhave a 45 degree bend 332 as shown in FIG. 18B, a 90 degree bend 334 asshown in FIG. 18C, or a 180 degree bend 336 as shown in FIG. 18D.Alternatively, more complex shapes may be employed. For example, thedistal tip section 312 may have a shepherd's hook shape 338 as shown inFIG. 18E, or an abbreviated shepherd's hook shape 340 (where the enddoes not curve out) as shown in FIG. 18F. Other shapes may be useddepending on the specific anatomy being navigated.

For purposes of accessing the OA via the ICA, particularly when the OAtake-off angle from the ICA is at a right angle or a slightly rearwardangle, the shepherd's hook 338 shown in FIG. 18E may have an overalllength L of approximately 10-15 mm and preferably about 12 mm; a primarycurve 342 radius R1 of approximately 7.5-15 mm and preferably about 10mm (to approximate one half the inside diameter of the ICA); and an arclength of approximately 35-55 degrees, preferably about 45 degrees; asecondary curve 344 radius R2 of approximately 2-3 mm and preferablyabout 2 mm (to approximate the inside diameter of the ICA) and an arclength of about 170 to 190 degrees and preferably 180 degrees; and atertiary curve 346 radius R3 1.0 mm and an arc length of about 15 to 30degrees. This configuration enables the distal tip 314 to cannulate theOA and the outside surface of the secondary curve rests against theopposite wall of the ICA. The tertiary curve 346 may be eliminated toform an abbreviated shepherd's hook shape 340 as shown in FIG. 18F inthe event the OA take-off angle is more rearward. The primary, secondaryand tertiary curves may be co-planar.

These shapes maybe pre-formed by the manufacturer or formed by thephysician during use utilizing heat-set techniques known in the art. Aunique heat-set technique discovered by the inventors may be employed toimprove shape retention. The technique involves placing the distal tipsection 312 over an annealed stainless-steel mandrel pre-formed to thedesired shape (e.g., abbreviated shepherd's hook). Alternatively, thedistal tip section 312 may be placed into a groove in a metal formingplate, where the groove pattern corresponds to the desired shape. Whileon the pre-formed mandrel on in the groove of the forming plate, thedistal tip section 312 is then exposed to heat (e.g., airflow) at orabove the mechanical relaxation point of the polymers. Since PTFE hasthe higher mechanical relaxation temperature of the polymers used, thetarget temperature may be selected to achieve mechanical relaxation ofthe rigid amorphous fraction (RAF) phase of PTFE, corresponding to atemperature range of approximately 210 to 250 degrees F. In thisexample, the distal tip section 312 is then exposed to airflow at 210 to230 degrees F. for 5 to 8 minutes. Immediately after heating, and whilestill on the pre-formed mandrel on in the groove of the forming plate,the distal tip section 312 is cooled below ambient temperature to lockin the desired shape. In this example, the distal tip section 312 isquenched in an ice bath approximating 32 to 45 degrees F. for 5 to 8minutes.

Rapid Exchange (RX) Aiming Microcatheter (AMC)

With reference to FIG. 19, the RX AMC 400 is shown schematically. The RXAMC 400 is similar in function as OTW AMC 300 described previously butis designed to facilitate exchange over a conventional length (e.g., 150cm) guidewire without the need for an exchange length (e.g., 300 cm)guidewire making it easier and faster for the physician. Whereas theguidewire exits the proximal end of the OTW AMC 300, the guidewire exitsa side port 405 in the RX AMC 400 located closer to the distal end, thusenabling the rapid exchange functionality. Because the guidewire exitport 405 is located closer to the distal end, the proximal shaft portion402 of the RX AMC 400 does not need to accommodate a guidewire, and thusmay comprise a solid core push wire (e.g., 304v stainless steel, springtemper) having an overall length of about 100 cm. A torque device 404may be disposed on the push wire 402 to manipulate the RX AMC 400 whenin use. The proximal end of the push wire 402 may be covered withpolyolefin heat shrink tubing to render it blunt. The push wire may havean outside diameter of 0.023″ for the proximal 90 cm, followed by ataper down to 0.010″ over the next 10 cm. The distal 1 cm or so may bestamped into a cupped ribbon having a width of 0.023″ and a thickness of0.003″ for insertion and attachment to the first distal shaft section408.

Distal tubular shaft sections 408, 410, 412, 414 and 416 may comprisemultilayered materials with gradually increasing flexibility in thedistal direction over an overall length of about 53 cm with an insidediameter of about 0.0165 in. to accommodate 0.010″ and 0.014″guidewires. First distal section 408, the proximal end of which definesthe guidewire port 405, may have a length of about 3 cm and an outsidediameter of 0.034″ comprising the following layers: polyester heatshrink (e.g., PET; inside diameter 0.055″; wall thickness 0.0005″) overa dual layer coil over a single layer braid over an inner liner. Thedual layer coil, single layer braid and inner liner may comprise thesame materials and construction as described with reference to the OTWAMC 300.

Extending from the first distal section 408, second distal section 410may have a length of about 5 cm and an outside diameter of about 0.034″comprising the same layers as first distal section 408 except the outerlayer may comprise a thermoplastic elastomer (e.g., PEBAX 7233;approximately 0.003″ wall thickness). Extending from the second distalsection 410, third distal section 412 may have a length of about 15 cmand an outside diameter of about 0.034″ comprising the same layers assecond distal section 410 except the outer layer may comprise a softerthermoplastic elastomer (e.g., PEBAX 5533; approximately 0.003″ wallthickness). Extending from the third distal section 412, fourth distalsection 414 may have a length of about 30 cm and an outside diameter ofabout 0.034″ comprising the same layers as third distal section 412except the outer layer may comprise an even softer thermoplasticelastomer (e.g., PEBAX 3533; approximately 0.003″ wall thickness).

From the fourth distal section 414, a distal tip section 416 extendsabout 1.5 cm with an outside diameter that tapers from 0.034″ to 0.0295″and with a minimum inside diameter of 0.016″. The distal tip section 416may comprise the same materials and construction as described withreference to distal extension 312 of the OTW AMC 300 and may be formedinto any of the shapes described with reference to FIGS. 18A-18F.

With reference to FIG. 19A which is a detailed view taken along circle Ain FIG. 19, further detail of the junction between push wire 402 and thefirst distal section 408 is shown schematically. To form this junction,the push wire 402 is loaded under the thermoplastic and reflowed, thencovered in PET.

Rapid Exchange (RX) Micro Balloon Catheter (MBC)

With reference to FIG. 20, the RX MBC 500 is shown schematically. RX MBCis similar to RX AMC 400 in that it is designed to facilitate exchangeover a conventional length (e.g., 150 cm) guidewire without the need foran exchange length (e.g., 300 cm) guidewire making it easier and fasterfor the physician. The guidewire exits a side port 510 in the MBC 500located closer to the distal end, thus enabling the rapid exchangefunctionality. Because the guidewire exit port 510 is located closer tothe distal end, the proximal shaft section 502 of the MBC 500 does notneed to accommodate a guidewire, and thus may comprise a single lumenhypotube (e.g., 304v stainless steel, spring temper, 112.5 cm length,0.017″ ID, 0.023″ OD, PTFE coated). The single lumen in the proximalshaft 502 may be used to inflate and deflate the balloon 520 via hub 504connected to an inflation device (not shown).

A mid-shaft section 506 (e.g., 7233 Pebax, 0.030″ ID, 0.003″ wallthickness) may extend approximately 17 cm from the proximal shaft 502,with about 10 mm overlapping and thermally bonded to the proximal shaft502. A core wire (not visible) (spring temper 304v stainless steel) mayextend about 18 cm from the proximal shaft 502 inside the mid-shaft 506,with about 5 cm of the proximal end of the core wire extending insidethe proximal shaft 502 and secured thereto by an interference fit. Thecore wire may have a nominal diameter of 0.010″ with the proximal 5 cmcenterless ground to 0.006″ diameter and bent at two 30-degree angles toform the interference fit with the inside surface of the proximal shaft502. The distal 3 cm of the core wire may be centerless ground to 0.004″diameter to provide a gradual stiffness transition across the guidewireexit port 510.

A distal shaft section 508 may extend approximately 30 cm from themid-shaft section 506, and the junction between the two may form theguidewire port 510. The distal shaft section 508 may include an inner514 and a distal outer 512 which are shown in more detail in FIGS.20A-20C. As shown in those figures, the inner 514 and the distal outer512 are co-axial. The inner extends from the guidewire port 510, throughthe balloon 520 to define a distal tip 518. The distal outer 512 extendsfrom the guidewire port 510 to the proximal end of the balloon 520. Atthe guidewire port 510, the inner 514 exits the distal outer 512, butotherwise extends inside the distal outer 512 and balloon 520.

To form the junction between the mid-shaft 506 and the distal shaft 508,the proximal end of the distal outer 512 may be square-cut with theinner 514 extending slightly proximal thereof. The distal end of themid-shaft 506 may be skive-cut at a 30 to 45 degree angle and positionedaround the distal outer 512 with the inner 514 projecting out therefrom.A round support mandrel may be placed in the inner 514 extending out theproximal end thereof. A crescent-shaped support mandrel may be insertedin the mid-shaft 506 extending out the distal end thereof into thedistal outer 512 with the inner 514 resting inside the saddle of thecrescent-shape. The junction may be thermally reflowed to create asealed thermal bond between the components with the inner 514 exitingthe outer 512 where the outer 512 and midshaft 506 come together.Optionally, this sealed junction may be configured to burst at apressure that is lower than the burst pressure of the balloon 520. Inthis manner, as the inflation pressure exceeds (by, e.g., 1-4 ATM) thenominally rated inflation pressure of the balloon 520 (i.e., thepressure at which the balloon reaches its specified inflated diameter),the sealed junction will burst rather than the balloon 520. When in use,a burst failure of the junction will harmlessly occur inside the guideor intermediate catheter (substantially proximal of the balloon), ratherthan at the balloon 520 inside the vasculature where a burst is lesssafe. This is particularly beneficial for a non-compliant balloon(growth rate of 4% to 6% over its working range (nominal to rated burstpressure)).

With reference to FIGS. 20A-20C, the details of the distal portions ofthe MBC 500 may be seen more clearly. FIG. 20A is a detailed view ofcircle A shown in FIG. 20; FIG. 20B is a detailed view of circle B shownin FIG. 20A, and FIG. 20C is a longitudinal sectional view taken alongline C-C in FIG. 20B. The distal outer 512 may comprise a thermoplasticelastomer (e.g., Pebax 5533 or 7233, 0.030″ ID, 0.003″ wall thickness).The inner 514 may comprise a multilayered construction with an innerliner 542 (e.g., etched PTFE, 0.00075″ wall), a coil middle layer 544(e.g., spring temper 304v stainless steel, 0.001″×0.005″ flat wire,0.0085″ pitch, 0.019″ ID, 20 cm length) and a thermoplastic elastomerouter layer 546 (e.g., Pebax 3533 0.029″ ID, 0.0015″ wall). The layers542, 544 and 546 may be thermally reflowed to bond each layer together.A tack bond 516 (e.g., 2 mm length, less than ⅓^(rd) circumference)between the outer 512 and inner 514 may be thermally formed to limitlongitudinal movement therebetween and transmit longitudinal pushforces.

The distal end of the distal outer 512 may be thermally bonded to theproximal waist 52 of the balloon 520. The distal waist 524 of theballoon 520 may be thermally bonded to a distal portion of the inner514, with approximately 5 mm to 7 mm of the inner 514 extending beyondthe distal waist 524 of the balloon 520 to form a distal tip section518. A radiopaque marker band 530 (e.g., PtIr 90/10, 0.5 mm to 1.0 mmlong) may be placed over the inner 514 under the balloon 520 at one ormore desired locations such as the proximal, middle or distal aspects ofthe inflatable portions of the balloon 520. Similarly, a radiopaquemarker band 532 may be placed around the distal tip section 518 of theinner 514. The distal marker band 532 may abut a distal terminus of thecoil layer 544 of the inner 514 to define an atraumatic distal tip(e.g., 1 mm length) free of the coil layer 544. Optionally, the distalterminus of the coil 544 may be annealed to prevent fraying.Additionally or alternatively, the marker band 532 may be swaged overthe distal terminus of the coil 544. As mentioned elsewhere herein, theextended distal tip section 518 acts like the tip of a microcatheter tofacilitate advancement over a guidewire around tight turns withoutcausing guidewire back-out for cannulation of the OA, for example.

Over-the-Wire (OTW) Micro Balloon Catheter (MBC)

With reference to FIGS. 20D and 20E, an OTW MBC 550 is shownschematically. The OTW MBC 550 is similar to the RX MBC 500 shown inFIG. 20, except that the OTW MBC 550 has a full-length guidewire lumen,thus it is referred to as an over-the-wire (OTW) configuration. Thisconfiguration of the OTW MBC 550, in contrast to the rapid exchangeconfiguration of the RX MBC 500, provides a lumen (i.e., guidewirelumen) that extends the full length of the device, thus it may be usednot only for advancement over a guidewire, but it may also be used forinfusion, aspiration and guidewire exchange once the OTW MBC 550 isdisposed intravascularly. Further, due to the microcatheter-likeconstruction of the OTW MBC 550 with a shapeable distal tip, it may beused like the OTW AMC 300 to steer and cannulate a desired targetvessel, and because it is torquable, it may be rotated back-and-forthwhile being advanced to improve its ability to cross tight restrictions.Thus, the OTW MBC 550 serves the dual purposes of a microcatheter (e.g.,OTW AMC 300 or RX AMC 400) and a balloon catheter (e.g., RX MBC 500) andthereby eliminates the need to exchange the microcatheter for theballoon catheter once the target vessel (e.g. OA) has been cannulated.

The OTW MBC 550 may include a manifold 552 with inflation and guidewireports. Extending from the manifold 552, a strain relief 554 may beprovided for connection the catheter shaft, starting with proximal shaftsection 556. The catheter shaft, including proximal shaft section 556,mid-shaft section 558 and distal shaft section 560, may comprise aninner disposed in an outer, wherein the inner defines a guidewire lumenand the annular space between the inner and outer defines an inflationlumen for a balloon 562. The distal end of the outer may be connected toa proximal waist of the balloon 562, while the inner extends through theballoon 562 to define a distal tip section 564, with the distal waist ofthe balloon 562 connected to the inner approximately 8-12 mm proximal ofthe distal end of the distal tip section 564. The distal tip section 564may be shaped as described with reference to FIGS. 18A-18F.

The inner may comprise the same or similar construction as the OTW AMC300, thus providing microcatheter-like performance. The outer maycomprise a series of increasingly flexible polymer tubes from proximalto distal. For example, the outer of the proximal shaft section 556 maycomprise a relatively stiff polymer (e.g., Pebax 7233, 75 cm length,0.030-0.034″ OD, 0.003 wall thickness), transitioning to the mid-shaftsection 558 comprising a relatively flexible polymer (e.g., Pebax 5533,40 cm length, 0.030-0.034″ OD, 0.003 wall thickness), and ending in thedistal shaft section 560 comprising an even more flexible polymer (e.g.,Pebax 3533, 30 cm length, 0.030-0.034″ OD, 0.003 wall thickness). Theballoon 562 may comprise the same material as balloon 520 with theproximal waist sized to fit inside the outer of the distal shaft section560. Radiopaque marker bands 566 may be provided on the inner adjacentthe proximal and distal ends of the body of the balloon 564, in additionto the distal aspect of the distal tip section 564.

Alternative Microcatheter

With reference to FIG. 21A, an alternative aiming microcatheter 610 isshown schematically in longitudinal cross-section. The microcatheter 610may include an elongate shaft 612 having a proximal or main shaftportion 611 and a distal tip section 613 a with a bumper tip 613 b. Alumen extends through the entire elongated shaft and the hub 614. Theoverall length of the proximal shaft section 611 may be approximately150 cm to 160 cm with a 10-15 mm distal section 613 a. The proximalshaft section 611 may have an outside diameter of approximately0.030-0.036 inches to fit within the aiming catheter (described later).The distal shaft section 613 a may have an outside diameter ofapproximately 0.029 inches to fit within the ophthalmic artery. Theinside diameter of the elongate shaft 612 may be approximately 0.0125inches to accommodate a 0.010-inch guidewire, or 0.015-0.016 inches toaccommodate a 0.014-inch guidewire. The elongate shaft 612 may have ahydrophilic coating along its distal 70 cm, for example. The elongateshaft 612 may be formed of variable durometer polymers along its lengthto impart increased flexibility in the distal direction, with embeddedmetallic braid and coils and a PTFE liner as will be described in moredetail.

The proximal end of the microcatheter 610 may include a hub 614connected thereto and a strain relief 615. The strain relief 615 may betapered from the hub 614 to the proximal shaft 611 as shown in FIG. 21Aor may be shaped ergonomically as shown in FIG. 22A to facilitaterolling between fingers to change the direction of the curved distaltip.

A torque handle 620 may be placed over the main shaft 611, the strainrelief 615 and/or hub 614 as shown in FIGS. 22B and 22C. The handle 620may include relatively larger proximal portion 622 and bulbous distalportion 624 to accommodate rolling by first and second fingers, and arecessed portion 626 to accommodate rolling by a thumb, for example. Thehandle 620 may include a through lumen 621 to accommodate the main shaft611 of the microcatheter 610, in addition to a proximal slot 623 toaccommodate wings of the hub 614, thereby facilitating torquetransmission from the fingers/thumb to the hub 614 and then to themicrocatheter 610 for purposes of steering a curved tip. This torquehandle 620 may engage the hub in other ways, such as snapping intopurpose-built features other than the hub wings.

The distal tip 630 of the microcatheter 610 may be straight or may becurve-shaped as shown in FIGS. 23A-23F. The distal tip 630 may be formedto have an anatomically relevant shape such as a 45-degree bend, a90-degree bend, a 180-degree bend, a shepherd's hook shape, or anabbreviated shepherd's hook shape (where the end does not curve out),for example. Other shapes may be used depending on the specific anatomybeing navigated. These shapes maybe pre-formed by the manufacturer or bythe physician during use, utilizing heat-set techniques known in theart. As shown in FIG. 23G, for purposes of accessing the ophthalmicartery via the internal carotid artery, particularly when the ophthalmicartery take-off from the internal carotid artery is at a right angle orslightly rearward, the shepherd's hook may have an overall length ofapproximately 1 cm, with a primary curve 632 height of about 2.5 mm (toapproximate one half the inside diameter of the internal carotid artery)and an arc length of about 45 to 90 degrees; a secondary curve 634height of about 5.0 mm (to approximate the inside diameter of theinternal carotid artery) and an arc length of about 60 to 120 degrees;and a tertiary curve 636 height of about 2.0 mm and an arc length ofabout 15 to 30 degrees such that the distal end cannulates theophthalmic artery and the outside surface of the secondary curve restsagainst the opposite wall of the internal carotid artery. The tertiarycurve 636 may be eliminated as shown in FIG. 23H in the event theophthalmic artery take-off is in a more rearward direction.

With reference to FIG. 21B, the proximal or main shaft section 611 isshown schematically in more detail. The inside of the main shaft section611 may comprise a liner 616 a of PTFE having an inside diameter of0.0165 inches and a wall thickness of 0.0075 inches, for example. Theliner 616 a may be stretched to 0.0130 inches inside diameter with awall thickness of 0.0005 inches, for example. The outside surface of theliner may be etched for adhesion of subsequent layers. The main shaftsection 611 may further include a braided support layer 617 a over theliner 616 a comprising spring-temper stainless steel ribbon sized at0.0005 inches by 0.0025 inches, braided at 175 picks per inch with a onewire under over two pattern or a 1/1 pattern, optionally with a chasewire, for example. The main shaft section 611 may further include, overthe braided support layer 617 a, a dual layer coil 618 a of helicalhollow strand 304v stainless steel wire, where the first layer comprises18 wires, 0.0012-0.0015 diameter wound to 0.022 outside diameter righthand wind, and where the second layer comprises 18 wires, 0.0014diameter wound to 0.025 inches outside diameter left-hand wind. The duallayer coil 618 a may be pressed such that the round wires become oval incross-section with a height of about 0.0012 inches. The main shaftsection 611 may further include, over the dual layer coil 618 a, apolymer jacket 619 a comprising various durometer polyether block amidetubing. The durometer may vary from 35D proximally to 72D distally. Thepolymer jacket 619 a may be heat-flowed over the underlying layers.

With reference to FIG. 21C, the distal tip section 613 a is shownschematically in more detail. The distal tip section 613 a may comprisea continuation of the liner 616 b of the main shaft section 611. Avariable pitch coil 617 b of platinum tungsten having an inside diameterof 0.019 inches wound from 0.0025 inch diameter wire may be placed overthe liner 616 b. A soft polymer jacket 619 b (e.g., 80A or 90A durometerthermoplastic polyurethane or 35D durometer polyether block amide) mayencapsulate the coil 617 b and liner 616 b. The PTFE liner 616 b maystop short of the distal end, where are the polymer jacket 619 b extendsto form a soft distal bumper tip 613 b. The distal tip section 613 a mayinclude three different regions where the coil has a different pitch. Inthe distal-most region, the coil may have a relatively tight pitch(e.g., no gap) to render the distal end more radiopaque such that thedistal end maybe readily identified under x-ray. By using a radiopaquecoil rather than a tubular radiopaque band, the distal tip is renderedmore flexible. The middle region may have a relatively looser pitch toimpart more flexibility and kink resistance. The proximal-most regionmay have a looser pitch than the distal-most region but a tighter pitchthan the middle region to provide for better torque transmission and totransition the stiffness to the proximal or main shaft section thatincludes braid.

With reference to FIG. 21D, the transition between the proximal or mainshaft section 611 and the distal tip 613 a is shown schematically inlongitudinal cross-section. In this transition region, the liner 616 a,616 b extends from the main shaft section to the distal tip sectionmaintaining the same inside diameter. The braid layer 617 a and the duallayer coil 618 a of the main shaft section 611 end in the middle of thetransition region, where the variable pitch coil 617 b of the distal tipsection 613 a begins. The polymer jacket 619 a, 619 b, like the liner616 a, 616 b, extends from the main shaft section 611 to the distal tipsection 613 a, but tapers in outside diameter as it crosses the junctionand eventually forms the distal bumper tip 613 b.

Alternative Balloon Catheter

With reference to FIG. 24A, a monorail type over-the-wire balloondilatation catheter 640 is shown in schematic longitudinalcross-section. The balloon catheter 640 may be used to dilate arestriction in the ophthalmic artery, for example. The balloon catheter640 may be navigated over a guidewire (not shown) from the femoralartery or radial artery, for example, to the ophthalmic artery. Ifnavigated from the femoral artery, the balloon catheter 640 may have anoverall length of approximately 160 cm, for example, and may include ahydrophilic lubricious coating. The balloon 642 may have variousdiameters such as 1.0 mm, 1.25 mm, 1.5 mm, 1.75 mm or 2.0 mm and variouslengths such as 0.5 cm, 1.0 cm or 1.5 cm for purposes of dilating arestriction in the ophthalmic artery.

As seen in FIG. 24B, the balloon 642 may have a tapered profile to mimicthe funnel-shaped geometry of the ophthalmic artery at its origin(ostium) at the internal carotid artery and into the short limb. Forexample, the balloon 642 may be stepped or tapered from 1.75 or 2.0 mmproximally to 1.25 or 1.5 mm distally, for example. The distal tip 643may have a length of 1.0 cm-1.5 cm and an outside diameter ofapproximately 0.015-0.025 inches, for example.

The shaft 641 balloon catheter 640 may include a proximal sectioncomprising a PTFE coated SST hypotube with a proximal hub. The shaft 641of the balloon catheter 640 may include a mid-section comprising apolymer tube with a tapered core wire extending therein. The proximalends of the mid-shaft polymer tube and core wire may be boded to thedistal end of the hypotube. The distal section of the shaft 641 maycomprise two coaxial tubes including an inner to define a guidewirelumen and an outer to define an inflation lumen. The inner extendsinside the outer from the distal end of the mid-shaft (proximalguidewire port for monorail design), through the balloon 642 and thedistal tip segment (distal guidewire port). The outer extends from thedistal end of the mid-shaft to the proximal end of the balloon 642.

The illustrated balloon catheter 640 differs from conventional designsin several aspects, including the distal tip segment 643 that provides astiffness transition zone between the distal end of the guidewire (wheninside the guidewire lumen and extending into the target artery) and thedistal waist of the balloon 642 where it is bonded over the inner. Whenin use, the bare distal portion of the guidewire is much more flexiblethan the distal waist of the balloon where it is bonded over the innerwith the guidewire inside. Because the take-off angle of the ophthalmicartery can be very sharp (right angle or rearward facing), conventionalballoon catheter designs tend to cause the guidewire to lose purchase inthe ophthalmic artery and slip out as the balloon catheter is advancedover the wire and into the ophthalmic artery. The flexible distal tipsegment 643 of the illustrated balloon catheter 640 provides atransition in flexibility: from the bare distal guidewire, to the distaltip segment with the guidewire therein, to the distal balloon waistwhere it is bonded to the inner with the guidewire therein.

Thus, the balloon catheter 640 has a microcatheter-like supported distaltip segment 643 to facilitate flexibility from the guidewire to theballoon 642, thereby facilitating placement of the tip 643 and balloon642 into the ophthalmic artery. In order to optimize this flexibility, acoiled structure with variable pitch as described previously maybeemployed. Among other advantages, the coil structure provides forflexibility transition, kink resistance, radiopacity and limited stiffsections (that conventional radiopaque marker bands tend to cause). Thedistal tip segment 643 of the balloon catheter 640 may be shaped asdescribed with reference to the curves 630 of the microcatheter 610.Thus, the balloon catheter 640 may function like a microcatheter,providing steering capability.

In general, the distal tip segment 643 maybe lined with either thinwalled polyimide or PTFE, with a polymer skim coat thereover to promotesubsequent adhesion of a polymer jacket thereover. The inside diametermaybe 0.013 inches for a 0.010-inch guidewire, tapered down to 0.011inches near the distal end, for example. Alternatively, the insidediameter maybe 0.017 inches for a 0.014-inch guidewire, tapered down to0.015 inches near the distal end, for example. The distal outsidediameter maybe less than 0.5 mm (0.020 inches) to allow access into theophthalmic artery, particularly if the ophthalmic artery has arestriction in its ostium.

With reference to FIG. 24C, the balloon 642 and tip 643 assembly isshown in more detail. The balloon 642 and tip 643 assembly may include acoil supported inner subassembly 644 that will be described in moredetail. The balloon 642 itself may be available in different sizes asdescribed previously. In this example, the platinum-tungsten coil in theinner 644 may have a variable pitch with a wide pitch proximally toimpart flexibility, a narrow pitch in the center 646 to impartradiopacity, a wide pitch distally to impart flexibility, and a narrowpitch at the very distal tip to impart radiopacity. With thisarrangement, the center of the balloon as well as the distal end will beclearly visible under x-ray. The outer 645 connected to the proximal andof the balloon 642 may comprise low durometer flexible tubing (e.g., 35Dor 55D polyether-block-amide, 80A polyurethane or 90A polyurethane).

Reference to FIGS. 24D and 24E, the distal tip segment 643 is shown inmore detail. Again, the distal tip segment 643 may be based on amicrocatheter-like design, thus enabling the balloon catheter 640 to beoptimized to navigate tortuous anatomy. As shown in FIG. 24D, the distaltip segment may comprise a PTFE liner 647 with a coil 648 a and apolymer jacket 649. The coil 648 a in the inner 644 may comprisestainless steel flat ribbon wire or round wire wound in a constant orvariable pitch to provide flexibility and kink resistance. Radiopaquemarker bands 646 comprising short metal tubes of platinum-iridium alloymay be embedded in the inner 644 at desired locations. Alternatively, asshown in FIG. 24E, the coil 648 b in the inner 644 may comprise platinumground wire with variable pitch. A wide pitch coil provides flexibilityand kink resistance, and a narrow pitch provides radiopacity wheredesired. The narrow pitch coil may be used to define radiopaque markersat desired locations such as the center of the balloon and distal end.Alternatively, radiopaque markers may be placed at the proximal anddistal ends of the balloon.

Guidewire

With reference to FIGS. 25A and 25B, a guidewire 650 is shownschematically. The guidewire 650 may include a proximal shaft 651 and adistal coil region 652. The guidewire 650 may be used to navigate to theophthalmic artery from the femoral artery or radial artery. If navigatedfrom the femoral artery, the guidewire 650 may have an overall length ofapproximately 200-300 cm, for example, and may include a hydrophiliclubricious coating over the distal 100 cm. The proximal portion 651 ofthe guidewire 650 may have a diameter of 0.014 inches for compatibilitywith 0.014-inch catheters, or 0.010 inches for compatibility with0.010-inch catheters. The distal portion 652 of the guidewire 650 mayhave an outside diameter of 0.008 inches, for example. The proximalportion 651 of the guidewire 650 may comprise a PTFE coated stainlesssteel wire 656. The distal portion 652 of the guidewire 650 may includecoils 654 a, 654 b having a length of approximately 2.0-6.0 cm over atapered core wire 653 extension of the proximal wire 656. A polymerjacket 655 may extend over the coiled region 652 and a portion of theproximal shaft 651.

In general, the illustrated guidewire 650 may be optimized for accessingthe ophthalmic artery and may be designed to maximize rail support forcatheters advanced over the guidewire into the ophthalmic artery, whichtends to have a sharp take-off angle from the internal carotid artery.As such, the distal portion 652 of the tapered wire core 653 under thecoils 654 a, 654 b may be much shorter than a typical guidewire. Withspecific reference to FIG. 25B, the tapered guide wire core 653 maytaper from 0.010 inches or 0.014 inches at the proximal end to 0.003inches over a length of approximately 2.0-6.0 cm such that the distalend of the guidewire 650 that is inserted into the ophthalmic arterywould have a wire core diameter of approximately 0.010 inches to 0.014inches when inserted 2.0-6.0 cm into the ophthalmic artery. In otherwords, the wire core diameter at the distal end would reach itsequivalent diameter at the proximal end after being inserted into theophthalmic artery 2.0-6.0 cm, corresponding to the short limb thereof.The coiled section 652 may comprise an internal coil 654 a and anexternal coil 654 b. The internal coil 654 a may comprise 0.001 inchdiameter platinum tungsten alloy wire or SST wire with an inside coildiameter corresponding to the wire core (approximately 0.003-0.004inches) and a length extending 1.0-3.0 cm from the distal end. Theexternal coil 654 b may comprise 0.001-0.002 inch diameter platinumtungsten alloy wire with an inside coil diameter of approximately 0.006inches and a length extending 2.0-6.0 cm from the distal end. Theinternal coil 654 a, external coil 654 b and wire core 653 may be weldedor soldered at the distal end to form a rounded tip, and the coils 654a, 654 b may be similarly bonded at their proximal end to the taperedwire core 653. A polymer jacket 655 having a wall thickness of0.0005-0.0010 inches may be placed over the coils 654 a, 654 b, thetapered core wire 653, and a portion of the proximal wire 656 having alength extending approximately 20.0 cm from the distal end.

Aiming Intermediate Catheter

With reference to FIG. 26A, a schematic illustration of an aimingintermediate catheter 660 is shown. The aiming intermediate catheter 660may include a shaft 661, a distal curve 662 and a proximal hub 663.Generally, the inside diameter of the aiming intermediate catheter 660is configured to accommodate the microcatheter and/or the ballooncatheter described previously, with the guidewire described previouslydisposed therein. An aiming sheath 670 (not shown), as will be describedwith reference to FIG. 27A, may be slidably disposed over the aimingintermediate catheter 660, and may be advanced or retracted to cover thedistal curve 662 of the aiming intermediate catheter 660 to effectivelychange the shape of the curve 662. The curve 662 may take any of theshapes described with reference to FIGS. 23A-23H, for example. Theaiming intermediate catheter 660 may be intended to facilitatenavigation to the internal carotid artery with its distal openingpointing to the ophthalmic artery such that devices inserted into andthrough the aiming intermediate catheter 660 are positioned to cannulatethe ophthalmic artery. In addition, the aiming intermediate catheter 660may be intended to facilitate safe navigation of the aortic arch,selective access of the great vessels (e.g., common carotid) from afemoral or radial approach, selective cannulation of the internalcarotid at the carotid bifurcation, or selective cannulation othervessels in the brain.

As seen in FIG. 26A, the aiming intermediate catheter 660 may have anoverall length of approximately 130 to 145 cm to facilitate navigationfrom the femoral artery to the ophthalmic artery. The tubular shaft 661of the aiming intermediate catheter 660 may have an outside diameter ofapproximately 0.049 inches to 0.052 inches and an inside diameter ofapproximately 0.038 inches. A catheter hub 663 and a strain relief maybe adhesively secured to the proximal end of the catheter shaft 661. Ahydrophilic coating may be applied to the working length of the cathetershaft 661.

As seen in FIG. 26B, which shows a longitudinal cross-section of theshaft 661, the proximal and of the catheter shaft 661 may comprise a0.00075 inch thick PTFE liner 664 over which a stainless steel braided665 a is secured with a polymer thermoplastic jacket 666 surrounding thebraid 665 a. The braid 665 a may comprise a diamond pattern with 80-125picks per inch and a length of 120-135 cm, using ultra-spring temper orHYTEN 304V stainless steel wire. The polymer jacket 666 may comprisemultiple sections of progressively flexible polymer such as 72Dpolyether-block-amide, 55D polyether-block-amide, 90AE polyurethane and80AE polyurethane (from proximal to distal). The distal 3-6 cm of thecatheter shaft 661 corresponding to the curve 662 may comprise acontinuation of the PTFE liner 664, over which a pattern-cut, NiTisuper-elastic alloy hypotube 665 b may be secured. A continuation of thepolymer thermoplastic jacket 666 of the proximal shaft may continue overthe distal shaft and extend slightly beyond the distal end of the PTFEliner 664 and pattern-cut NiTi hypotube 665 b to form a soft polymer tip667. The distal end of the NiTi hypotube 665 b may be plated withradiopaque material or a radiopaque marker band may be disposed thereonto facilitate visualization under x-ray.

An example of a cut pattern of the NiTi super-elastic alloy hypotube 665b is shown in FIG. 26C, where all dimensions are shown in inches. Asillustrated, the proximal end is at right and the distal end is at left,and the hypotube is shown splayed out flat rather than tubular. The wallthickness of the hypotube may be 0.002-0.003 inches and the strut widthmay be 0.0025 inches. The pattern may have 3 zones that areprogressively more flexible from proximal to distal by reducing theamount of material proximal to distal (e.g., increasing size of cuts,using a more sparse cut pattern, or using a different cut pattern ineach section). In this example, the graduated flexibility is provided byincreasing the longitudinal spacing between struts from 0.005, to 0.006to 0.0075 inches.

The shape of the distal curve 662 of the aiming catheter may be impartedby pre-forming the NiTi hypotube before assembly, and then by heatsetting the final assembly such that the polymer jacket 666 and PTFEliner 664 assume the same shape as the NiTi hypotube 665 b. I.e., Usingthe same disposition or shape in which the NiTi was originally formed tomaximize shape retention. The super-elastic NiTi hypotube 665 b may bemade using the following process. The desired pattern may be laser cutinto the NiTi hypotube and subsequently bead blasted to remove slag ordross from the laser cutting. The cut NiTi hypotube may be placed in aforming fixture have the desired shape. The forming fixture may be afixture that retains that outer diameter of the hypotube, a mandrelinside the hypotube, or a combination of the two. While in the formingfixture, the cut NiTi hypotube may be annealed at 300 C for 3 minutes inheated oven or salt bath, then heat set for 6-10 minutes at 500-510 C.The NiTi hypotube is then removed from heat source and immediatelyquenched in room temperature water. The heat set laser cut NiTi hypotubemay be electropolished or chemically etched to remove surface tarnish ordiscoloration due to heat exposure.

Aiming Catheter Sheath

With reference to FIG. 27A, an aiming catheter sheath 670 is shownschematically. The aiming catheter sheath 670 may be designed to beplaced over the aiming intermediate catheter 660 and may be advancedover the curved portion 662 to straighten the curve to varying degreesto obtain different angles of curvature. The aiming catheter sheath 670may include an elongated shaft 671, 672 having a length of approximately110 to 125 centimeters, with a proximal hub 673 and strain relief. Theoutside diameter of the shaft 671, 672 may be 0.068 inches to 0.072inches, and the inside diameter may be 0.058 inches to 0.059 inches.

As seen in FIG. 27B which shows a longitudinal cross-section of theproximal shaft 671 and distal shaft 672, the proximal shaft 671 mayinclude a 0.00075 inch thick PTFE liner 674 over which a braid 675 a isdisposed, covered by a polymer jacket 676. The braid 675 a may comprisea diamond pattern with 80-125 picks per inch and a length of 108-114 cm,using ultra-spring temper or HYTEN 304V stainless steel wire. Thepolymer jacket 676 may comprise multiple sections of progressiveflexibility such as 72D polyether-block-amide, 55Dpolyether-block-amide, 90AE polyurethane and 80AE polyurethane (fromproximal to distal). The distal section 672 of the shaft comprising thedistal 3.0 cm, for example, may include a continuation of the PTFE liner674 over which a stainless-steel coil 675 b of round or flat wire may bedisposed, covered by a continuation of the polymer jacket 676. The coilmay comprise 0.002 inch by 0.005 inch flat 304V stainless steel ribbonwith variable pitch sections including 0.0075 inch pitch for 1.25-2.5 cmproximal section, 0.010 inch pitch; 5.0-7.5 cm for midsection and 0.012inch pitch for 1.25-2.5 cm distal section. A radiopaque marker band 678may be placed over the liner 674 and embedded in the polymer jacket 676just distal of the coil 675 b. The polymer jacket 676 may extend beyondthe PTFE liner 674, the coil 675 b and the marker band 678 to form asoft distal tip 677.

An alternative distal section design is shown in longitudinalcross-section in FIG. 27C. In this alternative design, the wire coil isreplaced with a laser cut NiTi hypotube 675 c similar to the same usedin the aiming intermediate catheter 660. An example of a cut pattern foruse in this alternative design is shown in FIG. 27D. As illustrated, theproximal end is at right and the distal end is at left, and the hypotubeis shown splayed out flat rather than tubular. The wall thickness of thehypotube may be 0.003 inches and the strut width may be 0.0025 inches.The pattern may have 3 zones that are progressively more flexible fromproximal to distal. In this example, the graduated flexibility isprovided by increasing the longitudinal spacing between struts from0.006, to 0.0075 to 0.009 inches.

Aiming Intermediate Catheter and Sheath System

FIGS. 28A and 28B schematically illustrate how the aiming intermediatecatheter 660 and the aiming catheter sheath 670 may be used together. Asshown in FIG. 28A, the aiming intermediate catheter 660 is disposed inthe aiming catheter sheath 670 through a hemostasis valve 680 connectedto the proximal hub 673 of the sheath 670. As shown, the sheath 670 maybe retracted and or the aiming intermediate catheter 660 may be advancedsuch that the distal curved portion 662 of the aiming intermediatecatheter 660 is disposed distal of the sheath 670 and where the curvedportion 662 assumes its preset curvature. The aiming intermediatecatheter 660 may be retracted or the sheath 670 may be advanced toadjust the degree of curvature and to point the distal opening of theaiming intermediate catheter 660 in the desired direction such aspointing toward the ophthalmic artery while disposed in the internalcarotid artery. The degree of curvature may also be adjusted forpurposes of, for example, safe navigation of the aortic arch, selectiveaccess of the great vessels (e.g., common carotid) from a femoral orradial approach, selective cannulation of the internal carotid at thecarotid bifurcation, or selective cannulation other vessels in thebrain. As shown in FIG. 28B, for purposes of advancing the aimingintermediate catheter 660 to the desired location, the aimingintermediate catheter 660, while retracted in the sheath, may beadvanced over a 0.035 inch guidewire 685 as a system, for example,through a separate guide sheath or femoral sheath.

Aiming Intermediate Catheter Handle

To enable precise axial movement of the aiming intermediate catheter 660relative to the aiming catheter sheath 670, and thereby enable preciseadjustment and locking of the curvature 662, an aiming system handle 690may be used as shown in FIGS. 29A and 29B. With specific reference toFIG. 29A, the handle 690 may include a rotational knob 692 operablycoupled to the aiming intermediate catheter 660 in order to rotate theaiming intermediate catheter 660 and thereby steer the distal curvedsection 662. The handle 690 may also include a slider (orslider/rotational knob combination) 694 to control axial movement of theaiming catheter sheath 670 relative to the aiming intermediate catheter660 in order to adjust the degree of curvature of the curved portion662. The inner workings of the handle 690 may be better appreciated withreference to FIG. 29B. The handle may include a body portion 696 that isfixed axially to the aiming intermediate catheter 660 but allowsrotation of the aiming intermediate catheter 660 through the use of arotator 693. The rotational knob 692 is fixed to the aiming intermediatecatheter 660 such that rotation of the knob 692 causes rotation of theaiming intermediate catheter 660 relative to the body portion 696 andsheath 670. The slider 694 is axially movable relative to the handlebody 696 but is fixed to the sheath 670 such that pushing or pulling theslider 694 relative to the handle body 696 causes the sheath 670 to beadvanced or retracted, respectively, relative to the aiming intermediatecatheter 660 such that the curved portion 662 of the aiming intermediatecatheter 660 is selectively covered or exposed, respectively. Acorollary arrangement may be used alternatively where pushing or pullingthe slider 694 relative to the handle body 696 causes the aimingintermediate catheter 660 to be advanced or retracted, respectively,relative to the sheath 670 which remains fixed.

Guide Sheath

FIG. 30 shows a schematic longitudinal cross-section of a guide sheath700 that includes a distal section (S1) that is very flexible, a middlesection (S2) that has extra kink resistance, and a proximal section (S3)that is very pushable. The middle section with extra kink resistance maybe particularly useful when navigating from the aorta, through theaortic arch, into the common carotid artery. This zone tends to be verytortuous and can cause conventional guide sheaths to become oval (ratherthan round) or kink. If the guide sheath becomes oval or kinks, it tendsto seize or block devices inserted therein. To prevent the shaft frombecoming oval or kinking, the middle section may include a pattern cutNiTi hypotube 708 disposed between a liner 702 and a polymer jacket 706.The proximal and distal sections may include a braid 704 disposedbetween the liner 702 and the polymer jacket 706. The liner 702 maycomprise PTFE tubing with a wall thickness of 0.00075 inches. Thepolymer jacket 706 may be progressively flexible from proximal todistal, such as 72D nylon 12 on the proximal section, 72D-55Dpolyether-block-amide on the middle section, and 80AE-90AE polyurethaneon the distal section. The proximal section may have a length ofapproximately 20-40 cm, the middle section may have a length ofapproximately 30-40 cm, and the distal section may have a length ofapproximately 20-30 cm. The middle section, when the guide sheath 700 isplaced in-vivo, may be positioned in the aortic arch. To facilitatex-ray imaging to confirm that the middle section is in the aortic arch,radiopaque marker bands 703 may be embedded at both ends of the middlesection. A marker band 703 may also be embedded at the distal end of thecatheter.

Alternative Example Method

FIGS. 31A and 31B schematically illustrate use of some of the devicesdescribed herein with reference to the internal carotid artery (ICA) andthe ophthalmic artery (OA). FIG. 31A shows the ICA, cavernous sinus ofthe ICA, and the OA branching off the ICA at a sharp right or backwardfacing angle. FIG. 31B shows the OA in more detail, where the OAoriginates as a funnel-shaped ostium as it branches off the ICA andextends to angle A to define a short limb, which may be the target fortherapy. Each of the devices described herein may be configured to workcooperatively to reach the OA from a femoral access approach. Thelengths may be adjusted to accommodate different access approaches suchas a radial access approach, a cervical access approach, or anoculofacial artery approach, for example. The guide sheath 700 (notshown) may be configured to accommodate the aiming intermediate catheter660 and aiming catheter sheath 670, which in turn may be configuredaccommodate the microcatheter 610 or balloon catheter 640 (not shown),which in turn may be configured to accommodate the guidewire 610.

By way of example, the guide sheath 700 (not shown) may be used toprovide access from the femoral artery, through the aorta and aorticarch, to the carotid bifurcation over a 0.035 inch guidewire. The aimingintermediate catheter 660 and aiming catheter sheath 670 may be insertedthrough the guide sheath 700 over a 0.035 inch guide wire, and thecurvature 662 of the aiming intermediate catheter 660 may be adjusted(as described previously) to aim its distal opening toward the ostium ofthe OA. The 0.035 inch guidewire may be removed, and the 0.010 or 0.014inch guidewire 650 may be inserted into the aiming intermediate catheter660, either alone or with the microcatheter 610 or the balloon catheter640 loaded on the guidewire 650. With the aiming intermediate catheter660 pointed to toward the OA ostium, the guidewire 650 may be insertedinto the OA, optionally using a shaped tip of the microcatheter 610 tomake fine steering adjustments to the guidewire 650 until it cannulatesthe OA. Once the guidewire 650 is disposed in the OA, beyond angle A forexample, the microcatheter 610 may be inserted into the OA for deliveryof drugs or contrast media, for example. Similarly, the balloon catheter640 may be inserted over the guidewire 650 into the OA to dilate arestriction therein.

Alternative Access Sites

Each of the devices described herein may be configured to workcooperatively to reach the OA from an access site in the femoral artery.The diameters and lengths may be adjusted to accommodate differentaccess sites such as the radial, brachial, cervical or common carotidarteries. Less known or heretofore unknown access sites may also beused, such as access from the supra-orbital, supra-trochlear,superficial temporal or occipital arteries. With reference to FIG. 32A,some of these less known access sites and related arterial anatomy areshown schematically: common carotid artery (CCA), external carotidartery (ECA), occipital artery (OcA), facial artery (FA), posteriorauricular artery (PAA), maxillary artery (MA), superficial temporalartery (STA), supra-orbital artery (SOA), dorsal nasal artery andophthalmic artery (OA). The supra-trochlear artery (STrA, not shown) issimilarly situated to the SOA and may be collectively referred to asoculofacial arteries (a.k.a. frontal or facial arteries).

With reference to FIG. 32B, one of the oculofacial arteries such as theSTrA or SOA may be accessed adjacent the eyebrow to navigate devices ina retrograde direction directly to the OA as shown by the dotted line.With reference to FIG. 32C, the STA may be accessed adjacent the ear tonavigate devices in a retrograde direction down the ECA, around thecarotid bifurcation at the CCA, then in an antegrade direction up theICA to the OA as shown by the dotted line. With reference to FIG. 32D,the OcA may be accessed adjacent the occipital bone to navigate devicesin a retrograde direction in the OcA, down the ECA, around the carotidbifurcation at the CCA, then in an antegrade direction up the ICA to theOA as shown by the dotted line. Each of these access sites is relativelysuperficial allowing identification using digital palpation ortransdermal doppler ultrasound, percutaneous access without the need fora cut-down, and relatively simple closure by manual compression or by acompression device wrapped around the head.

With each of the access sites in the head, it may be desirable toposition the treating physician's hands outside the field of radiationused to image the cranial vasculature. As such, and with reference toFIG. 32E, the physician's hands may be placed below the neck, resting onthe patient's chest, for example. However, because the vascular accessdirection is inferior, it may be helpful to employ a reversing system820 that allows the physician to advance devices in a superior directionand redirect the devices in an inferior direction. The reversing system820 may be positioned for accessing the SOA or STrA as shown by system820A, the STA as shown by system 820B or the OcA as shown by system820C. The reversing system 820 may include a proximal manifold 822, acommon conduit 824 and a reversing manifold 826. The proximal manifold822 may be secured below the patient's neck proximate the chest. Thecommon conduit 824 may comprise a 10 F braid reinforced tube, forexample. The reversing manifold 826 may include a U-turn conduit,optionally with means to minimize friction such as roller bearings. Thereversing manifold 826 may be secured proximate the access site, using ahead band, for example. The reversing manifold 826 may incorporate micromotors with elements that could feed or torque a catheter to mimic thephysician's hands at the proximal manifold 822.

Also, with each of the access sites in the head, it may be desirable toprovide an aid in site closure. As a way to automate manual pressure,compression headgear 830 may be used as shown in FIG. 32F. Thecompression headgear 830 may include a focal pressure applicator 832 anda headband 836. The focal pressure applicator 832 may comprise aninflatable pad connected to a syringe (not shown) by tubing 834 andstop-cock 835. The headband 836 may comprise an elastic strap and mayincorporate an adjustment mechanism to loosen or tighten as desired. Thecompression headgear 830 may be placed to aid in closure of the SOA, theSTA or OcA with the focal pressure applicator 832 positioned over theaccess site and the headband 836 placed diametrically relative theretoas shown.

The access sites in the head, in particular the STA approach, have anumber of advantages in terms of speed, performance, safety and closure.With regard to speed, the shorter distance reduces time to reach thetarget anatomy. With regard to performance, the shorter distance allowsfor increased suction force and better manipulation of devices. Withregard to safety, the shorter distance to the target anatomy avoidsnavigation of the aortic arch which may be laden with plaque giving riseto embolic and dissection risks. With regard to closure, the proximityof the STA to the skull reduces potential complications. Thus, theaccess sites in the head may provide benefits to procedures other thandilating the OA. For example, the access sites may be used forcerebrovascular procedures such as in the treatment of acute stroke withmechanical thrombectomy or aspiration devices. In addition, the accesssites may be used for coronary procedures such as in the treatment ofcoronary artery disease with balloon angioplasty devices.

Oculofacial Approach

One of the challenges of the oculofacial approach is the small size ofthe supra-orbital artery and the supra-trochlear artery, which tend tobe approximately 1.0+/−0.25 mm. Compared to a femoral approach where thefemoral artery is approximately 7.0+/−0.5 mm at the access site, theoculofacial approach must be performed on a much smaller scale. However,it has several potential advantages. For example, whereas a femoral orradial approach requires navigation through the aortic arch and carotidarteries, the oculofacial approach does not, thus reducing the risk ofan embolic event. Also, the oculofacial approach leads directly to theOA and doesn't require selective steering into side branches.

With reference to FIGS. 33A-33D, the oculofacial approach is describedin more detail. As seen in FIG. 33A, one or more of the arteriesbranching distally off of the ophthalmic artery (OA), such as thesupra-orbital (SOA) artery or the supra-trochlear (STrA) artery, may beaccessed subcutaneously near the eyebrow, and devices may be deliveredin a retrograde direction to the OA, OA ostium or internal carotidartery (ICA) as seen in FIG. 33B. This approach may be used fordiagnostic purposes such as retrograde injection of contrast media toenable x-ray visualization (e.g., angiography) the OA, OA ostium or ICA.This approach may also be used to establish reverse flow as described inco-pending U.S. patent application Ser. No. 16/583,508. Further, thisapproach may be used therapeutic purposes such as retrograde insertionof a balloon catheter 640 beyond the central retinal artery (CRA) todilate the OA, OA ostium or ICA. Such uses of the oculofacial accesssite may be implemented alone or in combination.

In a percutaneous access technique, the SOA and/or the STrA may bepalpated and a needle 924 may be inserted into the artery followed by aguidewire. The needle may be removed from the artery leaving theguidewire in place. An introducer sheath 922 may be placed over theguidewire to maintain access, and the guidewire may be removed to makeroom for other devices such as a different guidewire, microcatheter orballoon catheter to be inserted. Alternatively, the guidewire may beleft in place and a microcatheter or balloon catheter may be insertedover it without the use of an introducer sheath, called a barebacktechnique. Because the SOA and STrA lead directly to the OA and thecalibers of the SOA and STrA are so small, a bareback technique may bepreferred (as compared to a femoral or radial approach that make use ofintroducers, sheaths and catheters for navigation). Under x-rayvisualization, a balloon catheter or other therapeutic intravasculardevice may be advanced beyond the central retinal artery (CRA) to dilatethe OA, OA ostium or ICA, for example.

In a cut-down access technique, the SOA and/or the STrA may be exposedthrough a skin incision. Under direct visualization, access to the SOAand/or the STrA may be accomplished with the aid of a support tool 926having a handle and a sling in which the artery can rest as shown inFIG. 33C. Using a conventional needle, a scalpel or a trocar needle 924as seen in FIG. 33D, the SOA and/or the STrA may be accessed. It may behelpful to advance the needle or trocar in one direction (e.g.,retrograde) while applying traction in the opposite direction (e.g.,antegrade). The bareback technique described before may then be used toadvance a balloon catheter or other therapeutic intravascular devicebeyond the central retinal artery (CRA) to dilate the OA, OA ostium orICA, for example, under x-ray visualization.

In addition to making use of the bareback technique due to limited spaceinside the SOA and STrA, it may be desirable to make use of a fixed-wireballoon catheter 930 because it has a very low profile. FIGS. 34A and34B are schematic illustrations of a fixed-wire balloon catheter 930 forthe oculofacial approach. With reference to FIG. 34A, which shows aschematic side view of the fixed-wire catheter 930, the catheter mayhave an overall length sufficient to extend from the SOA or STrAaccessed near the eyebrow to the ostium of the OA at the ICA, plussufficient length for manipulation outside the body by the treatingphysician.

With reference to FIG. 34B, which shows a schematic side sectional viewof the fixed-wire catheter, the catheter may generally include anelongate shaft 932 with a distally mounted balloon 934 and a flexibleguidewire-like tip 936. The shaft 932 may comprise a core wire 931 overwhich the proximal waist 933 of the balloon 934 extends to a proximalhub 938 to define an annular inflation lumen therein. The core wire 931may taper distally and a coil 937 of radiopaque wire may be disposedover the tapered core 931. A polymer jacket 935 may extend over the coil937 and may be bonded to the core wire 931 proximal of the coil 937. Thedistal waist of the balloon 934 may be bonded to the polymer jacket 935over the coil 937. By way of example, the balloon 934 may have a lengthof about 1.0-1.5 cm and distal tip 936 may have a length of about 10 mm.The distal tip 936 may have an outside diameter of about 0.008 inches,and the proximal shaft 932 may have an outside diameter of about 0.014inches. The coil 937 length may be about 2.0 cm and the overall workinglength of the fixed-wire catheter 930 may be about 30 cm, and ahydrophilic coating may be applied to the shaft and optionally theballoon.

As an alternative to a fixed-wire balloon catheter, an innerlessover-the-wire balloon catheter 940 may be used as schematicallyillustrated in FIGS. 35A-35G. The innerless over-the-wire ballooncatheter 940 eliminates the need for a separate inner tube by providinga seal between the distal end of the balloon catheter 940 and theguidewire 945 as seen in FIG. 35A, which is a schematic cross-sectionalview of the distal ends of the balloon catheter 940 and guidewire 945.As shown, the distal balloon 942 waist may include an inside collar 943that fluidly seals to a raised part 947 of the guidewire. As shown inFIG. 35B, which is a schematic sectional view of the proximal end of theballoon catheter 940 and the guidewire 945, a Tuohy Borst fitting mayseal onto a proximal portion of the guidewire 945 and may be connectedto the proximal hub 944 of the balloon catheter 940 via a luer lockfitting (shown disconnected). Inflation and deflation of the balloon 942may be facilitated by connecting a syringe (not shown) or the like to aside port of the Tuohy Borst fitting.

As seen in FIG. 35C, which is a schematic partially sectioned side viewof the guidewire body 946 and tip 948, the guidewire 945 may comprise astandard design except for the provision of a raised portion 947 havinga slightly larger diameter (e.g., 0.016 inches) than the guidewire shaft(e.g., 0.010 inches). The raised portion 947 may comprise a short SSThypotube or polyimide tube having an inside diameter of about 0.013inches and a wall thickness of about 0.0015 inches boned to theguidewire proximal of the distal tip 948 of the guidewire 945, such asnear the proximal end of the coiled tip 948, as shown in FIG. 35D whichis a cross-sectional view taken along line B-B in FIG. 35C. As seen inFIG. 35E, which is a schematic sectioned side view of the balloon 942and catheter shaft 941 distal portion, an inner collar 943 is providedat the distal end of the balloon 942 to seal onto the raised portion 947of the guidewire 945 and eliminate the need for a separate inner tube.The proximal catheter shaft 941 may comprise a NiTi hypotube or 90AEpolyurethane tubing having an outside diameter of about 0.021-0.022inches. As shown in FIG. 35F which is a cross-sectional view taken alongline A-A in FIG. 35E, the inner collar 943 may comprise an outer layerof 0.001 inch wall thickness polyether-block-amide or polyurethane overan inner layer of 0.0005-0.001 inch wall thickness polyimide tubing fora combined wall thickness of about 0.0015-0.002 inches, an insidediameter of 0.0165 inches and an outside diameter of about 0.0195inches. The inner collar 943 may be bonded inside the distal waist ofthe balloon 942, which may be formed of a soft urethane extrusion have awall thickness of 0.001 to 0.002 inches and an outside diameter of about0.023-0.026 inches.

With reference to FIG. 35G, which is a schematic illustration of how theinnerless over-the-wire balloon catheter 940 may be used, an accesssheath is shown accessing the SOA, but may alternatively access theSTrA. The guidewire 945 may be inserted into the access sheath followedby the innerless balloon catheter 940 thereover, or the guidewire 945and innerless balloon catheter 940 may be inserted into the accesssheath together. The guidewire 945 and innerless balloon catheter 940may be advanced in the SOA or STrA to the OA until the distal end 948 ofthe guidewire 945 is disposed in the ICA. With the raised portion 947 ofthe guidewire 945 positioned just distal of the area to be dilated, suchas the ostium of the OA to the ICA, and the inner collar 943 of theinnerless balloon catheter 940 positioned on the raised portion 947 ofthe guidewire 945 to establish a fluid seal, the balloon 942 may beinflated to dilate a restriction is the OA, for example.

The oculofacial approach may be used in combination with a femoral orradial approach, an example of which is shown in FIG. 36A. The STrAand/or SOA may be accessed and cannulated with a microcatheter 960,which is similar to microcatheter 610 illustrated in FIG. 21A butforeshortened for the oculofacial approach. The microcatheter 960 mayinclude a relatively larger soft bulbous tip 965 on the distal end of anelongate shaft 962 as shown in FIG. 36B. The microcatheter 960 may bepositioned with its distal tip 964 in the OA beyond the branch to theCRA such as in the long limb of the OA. The microcatheter 960 may beused to deliver drugs, to inject contrast media or to aspirate the OAduring and/or after balloon dilation by applying a proximal vacuum. Anocclusion balloon catheter 950 may be inserted through the microcatheter960 with the occlusion balloon positioned distal of the CRA such as inthe long limb of the OA. The occlusion balloon catheter 950 may be usedto stop antegrade flow in the OA by inflating the occlusion balloon,thereby mitigating emboli flowing into the CRA and potentially causingharm to the retina. By using the oculofacial retrograde approach forthese purposes, the femoral or radial antegrade approach remains free todeliver the aiming intermediate catheter 660, microcatheter 610 orballoon catheter 640 (not shown) over guidewire 650 to deliver fluids orto dilate a proximal portion of the OA such as the ostium of the OA orthe OA short limb.

Superficial Temporal Artery Approach

With reference to FIG. 37, examples of devices used for the STA accessapproach are shown schematically. A procedural sheath 1172 may beinserted into the STA over an 0.035″ guidewire (not shown) having aknuckled end until the distal end of the procedural sheath 1172 ispositioned near the ECA and the proximal end of the procedural sheath ispositioned near the STA access site adjacent the tragus of the ear. Aguide sheath 1174 may be inserted into the procedural sheath 1172 andnavigated inferiorly down the ECA, around the carotid bifurcation to theICA until the distal end of the guide sheath 1174 is positionedsuperiorly to the carotid bifurcation. Optionally, the guide sheath 1174may be advanced through the STA and ECA without a procedural sheath1172. Also, optionally, the guide sheath 1174 may be advanced over anobturator and guidewire as described later. A microcatheter 1176 maythen be inserted into the guide sheath 1174 together with a guidewire1178 and navigated superiorly in the ICA until the distal end of themicrocatheter is positioned at or near the OA ostium. With the distalend of the microcatheter 1176 aimed toward the OA, the guidewire 1178may be advanced until the distal end of the guidewire is inside the OA.The microcatheter 1176 may be removed leaving the guidewire 1178, guidesheath 1174 and procedural sheath in place. A balloon dilation catheter(not shown) as described previously may be advanced over the guidewire1178 to the OA for dilation of a restriction therein.

With reference to FIG. 38A, an example of a guide sheath 1180 system isshown schematically. The guide sheath 1180 system may be used with theSTA approach described above. The guide sheath system 1180 may include aprogressively flexible braid and/or coil reinforced tubular guide sheath1184 placed over a tubular obturator 1186 placed over a guidewire 1188.To facilitate the “U” turn around the carotid bifurcation, the guidesheath system 1180 may use a straight guide sheath 1184A and a U-shapedobturator 1186A as shown in FIG. 38B. Alternatively, to facilitate the“U” turn around the carotid bifurcation, the guide sheath system 1180may use a U-shaped guide sheath 1184B and a straight obturator 1186B asshown in FIG. 38C. With either embodiment, the obturator 1186 may beselectively advanced or retracted relative to the guide sheath 1184 toeffectuate different curves while steering around the “U” turn at thecarotid bifurcation. In both embodiments, the curve may be approximately180+/−45 degrees with a radius of curvature of about 1.0 to 2.5 cm, byway of example, not necessarily limitation.

The guide sheath 1184 may be equipped with a pair of radiopaque markerbands 1185 that reside on the same transverse plane when the curve ofthe guide sheath 1184 is correctly positioned around the “U” turn at thecarotid bifurcation. In addition, the guide sheath 1184 may include apair of anchoring balloons 1183 similarly positioned as marker bands1185. As shown in FIG. 38D, the anchoring balloons 1183 may be placed ona straight guide sheath 1184A, or, as shown in FIG. 38E, the anchoringballoons 1183 may be placed on a curved guide sheath 1184A. Inflation ofthe anchoring balloons 1183 secures the distal portion of the guidesheath 1184 across the carotid bifurcation such that devices advancedtherethrough do not cause the guide sheath to back out of the ICA.

As an alternative the guide sheath 1184 include push/pull wires toprovide a steerable tip. As a further alternative, the guide sheath 1184may incorporate a straight or curved core wire disposed in a side lumenthat may be advanced or retracted to adjust stiffness to provideadditional support (core wire advanced) or flexibility (core wireretracted), and may include a curved shape to support the U-shaped curvearound the carotid bifurcation.

By way of example, not necessarily limitation, the following stepsdescribe the STA approach in more detail.

-   -   1) Locate the artery near the tragus of the ear.    -   2) Use ultrasound or echo to locate the artery for puncture.    -   3) Puncture the vessel with a Micro puncture kit (0.014″        compatible).    -   4) Insert an 0.014″ guidewire (that is predisposed to        “knuckling”, J-ing or prolapsing) through the micro puncture        needle.    -   5) Knuckle or for a “J” at the distal end of the guidewire.    -   6) Spin the guidewire to track through the STA to the ECA and        ultimately past the bifurcation into the CCA, using the wire to        straighten extreme tortuosity along the vessel(s).    -   7) Remove the needle and insert a 5 F/6 F procedural sheath with        dilator over the guidewire into the STA beyond any tortuosity        that would prevent advancing subsequent devices.    -   8) Remove the dilator and guidewire leaving the procedural        sheath in place. If the dilator was not able to be placed beyond        tortuosity that would prevent subsequent device exchanges, leave        the 0.014 guidewire in place in the CCA to maintain access.    -   9) Use below techniques to cross the carotid bifurcation        -   a. Insert a guiding sheath, obturator and 0.021-0.025″ angle            tip guidewire, steer the guidewire into the ICA and follow            the guidewire with the guide sheath.        -   b. Optionally, two microcatheters or a microcatheter and            guidewire may be used for additional rail support of the            guiding sheath further into the ICA.        -   c. Use either the curved-tip guide sheath with straight            obturator or curved-tip obturator with straight guide            sheath. As an alternative, use a steerable guiding sheath            placed at the carotid bifurcation and point the internal            lumen of the guide sheath preferentially towards the lumen            of the ICA. As a further alternative, use a flow directed            wire/catheter placed in the bifurcation and blood flow from            the common carotid to preferentially steer the flow directed            catheter from the ECA to the ICA, then use the flow directed            catheter as a rail to deliver the guide sheath into the ICA.        -   d. Verify the radiopaque markers are on one either side of            the bifurcation. If the 0.014″ guidewire was left in place            to maintain access, track the guide sheath over the 0.014″            guidewire into the CCA before swapping out to a            0.021″−0.025″ guidewire.        -   e. If the guide sheath incorporates inflatable anchoring            balloons, inflate the balloons to stabilize the curve and            provide flow cessation/allow aspiration during the            intervention.    -   10) Advance a curved-tip aiming microcatheter into the guide        sheath together with an 0.014 guidewire and navigated superiorly        in the ICA until the distal end of the microcatheter is aimed at        the OA ostium.    -   11) Advance the guidewire inside the OA.    -   12) Remove the microcatheter leaving the guidewire in place    -   13) Advance a balloon dilation catheter over the guidewire to        the OA    -   14) Place balloon across restriction in OA and inflate.    -   15) Deflate balloon.    -   16) Remove devices in reverse order, optionally applying        aspiration using guide sheath.    -   17) Close access site.

Identification of Dormant Photoreceptors

Identification of dormant photoreceptors may be used as a diagnosticstep before treating arterial disease in the vascular blood supply tothe rear of the eye (e.g., restriction in OA ostium, OA short limb,etc.). If dormant photoreceptors are present, improving blood flow tothe choroid may more likely be effective, as compared to photoreceptorsthat are atrophied or otherwise not dormant. As such, as a diagnosticstep, if dormant photoreceptors are found to be present in a givenpatient, then the patient may be treated using the devices and methodsdescribed herein. Absent dormant photoreceptors, the patient may not betreated using the devices and methods described herein or may be treatedwith alternative methods. In this diagnostic method, Optical CoherenceTomography (OCT) may be used to identify the presence or absence ofdormant photoreceptors in the macula. FIG. 39 shows the various tissuelayers visible with OCT.

The present method uses two forms of OCT to examine the fovea to lookfor possible dormant photoreceptors: en face OCT and B scan (e.g.,cross-sectional) OCT as shown in FIG. 40. Geographic atrophy appears asa light segment in the macula when viewed by en face OCT. In severecases, the majority of the macula may appear lighter than thesurrounding retina. Darker spots or areas in the macula, in particularin the foveal section, may correlate to dormant photoreceptors. Thefirst step is to take an en face OCT scan. An en face scan takes animage of the fovea, macula and majority of the retina looking directlyat it. This scan will be examined to identify a ‘darker’ spot at thefovea as indicated by the white arrow in the top en face image (see FIG.40 Panel A). If dormant photoreceptors (DP) are present, the centralfovea will appear darker than the surrounding macula tissue. The nextstep is to take an B scan using OCT. The B scan takes a cross section ofthe eye tissue and includes the layers from the retina to the choroid.This scan is also used to identify dark areas of tissue just below thefoveal pit as indicated by the white arrow in the top B scan image tothe right (see FIG. 40 Panel B). In the event DP are not present, thiswill be indicated by an absence of a dark spot as noted by the whitearrows in the en face and b scans on the bottom image as compared to theabove scans (see FIG. 40 Panels C and D).

The image comparison may be performed manually by a physician or OCTreader, or may be automated by an algorithm that examines each B scan,looks for the dark tissue segment, scans the en face image, looks forthe dark tissue segment and then finally compares the two to calculate alikelihood of the presence of dormant photoreceptors. FIG. 41 shows aflow diagram of an example process algorithm 1210 that may be automatedwith software run by a computer. Initially, an en face OCT image isacquired 1211 of the patient's eye under evaluation for treatment by thedevices and methods described herein. B scan images are then acquired1212 from the same eye. Dark areas in en face image are then identified1213. The corresponding B scan images (B scan slices that go throughdark area in en face image) are then selected 1214. In each of theselected B scan images, dark areas (A) are identified 1215. Also, ineach of the selected B scan images, the layer (L) is identified thatcontains photoreceptors 1216. A comparison 1217 is then made todetermine if the dark areas (A) reside within the layer (L) containingthe photoreceptors. If most of A resides in L, then dormantphotoreceptors are present, and the treatment described herein may beindicated 1218. Otherwise, the treatment described herein may not beindicated 1219 and alternative treatment options may be sought.

We claim:
 1. A microcatheter, comprising: a shaft having variableflexibility along a length thereof, the shaft including: a multilayeredproximal section including a proximal section outer layer; amultilayered mid-section including a mid-section outer layer that ismore flexible than the proximal section outer layer; a multilayereddistal section including a distal section outer layer that is moreflexible than the mid-section outer layer, and a braid; and a distal tipincluding a variable pitch coil, the variable pitch coil having a distalclosed-gap pitch, a proximal open-gap pitch, and a middle open-gap pitchgreater than the proximal pitch, a distal end of the variable pitch coilterminating proximally of a distalmost end of the distal tip, whereinthe braid of the distal section terminates at a distal end of the distalsection and abuts a proximal end of the variable pitch coil.
 2. Themicrocatheter of claim 1, wherein an outer diameter of the distal tip istapered toward the distal end of the distal tip.
 3. The microcatheter ofclaim 1, wherein the multilayered distal section includes a dual-layercoil of helical hollow strands, wherein the helical hollow strands havean elliptical cross-sectional shape.
 4. The microcatheter of claim 1,wherein the proximal section outer layer includes a polymer, and whereinthe multilayered proximal section further includes a dual-layer coilcomprising a helical hollow strand of wire, a single-layer braid, and aninner liner.
 5. The microcatheter of claim 4, wherein the mid-sectionouter layer includes a polymer that is more flexible than the polymer ofthe proximal section outer layer, and wherein the multilayeredmid-section further includes the dual-layer coil comprising the helicalhollow strands of wire, the single-layer braid, and the inner liner. 6.The microcatheter of claim 5, wherein the distal section outer layerincludes a polymer that is more flexible than the polymer of themid-section outer layer, and wherein the multilayered distal sectionfurther includes the dual-layer coil comprising the helical hollowstrands of wire, the single-layer braid, and the inner liner.
 7. Themicrocatheter of claim 6, wherein the distal tip further includes adistal tip outer layer.
 8. The microcatheter of claim 7, wherein a wallthickness of the distal tip outer layer is greater than a wall thicknessof the distal section outer layer.
 9. A microcatheter, comprising: ashaft having variable flexibility along a length thereof, the shaftincluding: a multilayered proximal section; a multilayered mid-sectionthat is more flexible than the multilayered proximal section; amultilayered distal section that is more flexible than the multilayeredmid-section, the multilayered distal section including: a distal sectionouter layer; a dual-layer coil having an inner coil layer and an outerlayer coil; a single-layer braid; and an inner liner; and a distal tipincluding: a distal tip outer layer; a single-layer coil having a distalclosed-gap pitch, a proximal open-gap pitch, and a middle open-gap pitchgreater than the proximal pitch, wherein the single-layer coilterminates proximally of a distalmost end of the distal tip; and theinner liner, wherein a distal-most end of the single-layer braid abutsthe proximal end of the single-layer coil at an abutment, wherein theouter layer coil of the dual-layer coil extends over the abutmentbetween the single-layer braid and the proximal end of the single-layercoil, and the inner layer coil of the dual-layer coil terminates at theabutment between the single-layer braid and the proximal end of thesingle-layer coil, and wherein, in a first configuration, a centrallongitudinal axis of the distal tip extends along a straight line,while, in a second configuration, the central longitudinal axis of thedistal tip is curved.
 10. The microcatheter of claim 9, wherein an outerdiameter of the distal tip is tapered toward the distal end of thedistal tip.
 11. The microcatheter of claim 9, wherein the dual-layercoil is formed of helical hollow strands of wire, wherein the helicalhollow strands of wire have an elliptical cross-sectional shape.
 12. Themicrocatheter of claim 9, wherein the multilayered proximal sectionincludes an outer layer formed of a polymer, the dual-layer coilcomprising the helical hollow strands of wire, the single-layer braid,and the inner liner.
 13. The microcatheter of claim 12, wherein themultilayered mid-section includes an outer layer that includes a polymerthat is more flexible than the polymer of the outer layer of theproximal section, and wherein the multilayered mid-section furtherincludes the dual-layer coil comprising the helical hollow strands ofwire, the single-layer braid, and the inner liner.
 14. The microcatheterof claim 13, wherein the distal section outer layer includes a polymerthat is more flexible than the polymer of the mid-section outer layer.15. The microcatheter of claim 14, wherein the distal tip outer layerincludes a polymer having a wall thickness that is greater than a wallthickness of the polymer of the distal section outer layer.
 16. Amicrocatheter, comprising: a shaft having variable flexibility along alength thereof, the shaft including: a proximal section including asolid core push wire and an outer layer; a plurality of distal sectionsincluding: a first multilayered distal section having a guidewire portat a proximal end; a second multilayered distal section extending fromthe first multilayered distal section, the second distal multilayeredsection being more flexible than the first multilayered distal section;a third multilayered distal section extending from the secondmultilayered distal section, the third multilayered distal section beingmore flexible than the second multilayered distal section; and a fourthmultilayered distal section extending from the third multilayered distalsection, the fourth multilayered distal section being more flexible thanthe third multilayered distal section; and a distal tip including avariable pitch coil having a distal closed-gap pitch, a proximalopen-gap pitch, and a middle open-gap pitch greater than the proximalpitch.
 17. The microcatheter of claim 16, wherein the outer layer of theproximal section is formed of a polyolefin heat shrink tubing.
 18. Themicrocatheter of claim 16, wherein a diameter of the push wire of theproximal section tapers distally from 0.023″ to 0.010″.
 19. Themicrocatheter of claim 16, wherein the distal tip section includes ashape profile, wherein the shape profile includes any one of a straightline, a line with a 45° bend, a line with a 90° bend, a line with a 180°bend, a shepherd's hook, or an abbreviated shepherd's hook.
 20. Themicrocatheter of claim 16, wherein the distal tip section is formed intoa shape of a shepherd's hook having a first curve in a first direction,and a second curve in a second direction that is different from thefirst direction, wherein the second curve extends from a distal end ofthe first curve.